Quantitation and Mass Spectrometric Data of Drugs and Isotopically Labeled Analogs

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Author: Ray H. Liu | Dennis V. Canfield | Sheng-Meng Wang

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Quantitation and Mass Spectrometric Data of Drugs and Isotopically Labeled Analogs

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© 2010 by Taylor and Francis Group, LLC

Quantitation and Mass Spectrometric Data of Drugs and Isotopically Labeled Analogs Ray H. Liu Sheng-Meng Wang Dennis V. Canfield With the assistance of Meng-Yan Wu and Bud-Gen Chen Fooyin University and

Robert J. Lewis and Roxane M. Ritter U.S. FAA Civil Aerospace Medical Institute

Boca Raton London New York

CRC Press is an imprint of the Taylor & Francis Group, an informa business

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CRC Press Taylor & Francis Group 6000 Broken Sound Parkway NW, Suite 300 Boca Raton, FL 33487-2742 © 2010 by Taylor and Francis Group, LLC CRC Press is an imprint of Taylor & Francis Group, an Informa business No claim to original U.S. Government works Printed in the United States of America on acid-free paper 10 9 8 7 6 5 4 3 2 1 International Standard Book Number: 978-1-4200-9497-8 (Hardback) This book contains information obtained from authentic and highly regarded sources. Reasonable efforts have been made to publish reliable data and information, but the author and publisher cannot assume responsibility for the validity of all materials or the consequences of their use. The authors and publishers have attempted to trace the copyright holders of all material reproduced in this publication and apologize to copyright holders if permission to publish in this form has not been obtained. If any copyright material has not been acknowledged please write and let us know so we may rectify in any future reprint. Except as permitted under U.S. Copyright Law, no part of this book may be reprinted, reproduced, transmitted, or utilized in any form by any electronic, mechanical, or other means, now known or hereafter invented, including photocopying, microfilming, and recording, or in any information storage or retrieval system, without written permission from the publishers. For permission to photocopy or use material electronically from this work, please access www.copyright.com (http://www.copyright.com/) or contact the Copyright Clearance Center, Inc. (CCC), 222 Rosewood Drive, Danvers, MA 01923, 978-750-8400. CCC is a not-for-profit organization that provides licenses and registration for a variety of users. For organizations that have been granted a photocopy license by the CCC, a separate system of payment has been arranged. Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for identification and explanation without intent to infringe. Visit the Taylor & Francis Web site at http://www.taylorandfrancis.com and the CRC Press Web site at http://www.crcpress.com

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Contents Foreword --------------------------------------------------------------------------------------------------- vii Preface ------------------------------------------------------------------------------------------------------- ix About the Authors ------------------------------------------------------------------------------------------ xi PART ONE ISOTOPICALLY LABELED ANALOG AS INTERNAL STANDARD FOR DRUG QUANTITATION — METHODOLOGY Chapter 1. Quantitation of Drug in Biological Specimen — Isotopically Labeled Analog of the Analyte as Internal Standard ............................................................................ 3 INTRODUCTION ................................................................................................................ Significance of Accurate Quantitation ................................................................................. Preferred Calibration Method .............................................................................................. I. INTERNAL STANDARD AND QUANTITATION IONS ............................................... A. Inadequate Isotopic Purity — An Extrinsic Factor ........................................................ B. Cross-Contribution Derived from Ion Fragmentation Mechanism — An Intrinsic Factor .......................................................................................................... II. FITTING CALIBRATION DATA ...................................................................................... III. 2H- VERSUS 13C-ANALOGS AS INTERNAL STANDARDS ........................................ CONCLUDING REMARKS ............................................................................................... REFERENCES ...................................................................................................................

3 3 4 4 4 5 6 7 9 10

Chapter 2. Isotopically Labeled Analog of the Analyte as Internal Standard for Drug Quantitation — Chemical Derivatization and Data Collection and Evaluation ............... 11 INTRODUCTION .............................................................................................................. I. CHEMICAL DERIVATIZATION .................................................................................... A. Production of Most Favorable Ion-Pairs for Drug Quantitation .................................. B. Exemplar Studies .......................................................................................................... C. Isotopically Labeled Analogs and Chemical Derivatization Groups ........................... II. ION INTENSITY CROSS-CONTRIBUTION DATA ..................................................... A. Full-Scan Mass Spectra ................................................................................................ B. Selected Ion Monitoring and Calculation of Ion Cross-Contribution Data ................. 1. Direct Measurement ................................................................................................ 2. Normalized Direct Measurement ............................................................................ 3. Internal Standard Method ........................................................................................ 4. Standard Addition Method ...................................................................................... C. Assessing the Accuracy of Empirically Determined Cross-Contribution Data ........... 1. Empirically Observed Concentration ...................................................................... 2. Theoretically Calculated Concentration .................................................................. 3. Comparing Empirically Observed and Theoretically Calculated Concentrations — Graphic Presentation .................................................................................. 4. Summary ..................................................................................................................

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11 12 12 12 13 13 17 18 18 19 20 20 21 22 24 25 26

III. COMPILATION OF FULL-SCAN MASS SPECTRA AND ION INTENSITY CROSS-CONTRIBUTION TABLES ................................................................................ A. Derivatization Procedures, Instrumentation, and Analytical Parameters .................... B. Collection of Mass Spectrometric Data ....................................................................... C. Ion Intensity Cross-Contribution Data ......................................................................... CONCLUDING REMARKS ............................................................................................. REFERENCES ...................................................................................................................

26 26 26 27 28 28

PART TWO MASS SPECTRA OF COMMONLY ABUSED DRUGS AND THEIR ISOTOPICALLY LABELED ANALOGS IN VARIOUS DERIVATIZATION FORMS Table of Contents for Appendix One ..................................................................................... 33 Figure I. Stimulants .................................................................................................................... Figure II. Opioids ..................................................................................................................... Figure III. Hallucinogens ......................................................................................................... Figure IV. Depressants/Hypnotics ........................................................................................... Figure V. Antianxiety Agents .................................................................................................. Figure VI. Antidepressants ....................................................................................................... Figure VII. Others ....................................................................................................................

35 129 217 251 273 327 349

PART THREE CROSS-CONTRIBUTIONS OF ION INTENSITY BETWEEN ANALYTES AND THEIR ISOTOPICALLY LABELED ANALOGS IN VARIOUS DERIVATIZATION FORMS Table of Contents for Appendix Two ................................................................................... 375 Table I. Stimulants ................................................................................................................... Table II. Opioids ...................................................................................................................... Table III. Hallucinogens ........................................................................................................... Table IV. Depressants/Hypnotics ............................................................................................. Table V. Antianxiety Agents .................................................................................................... Table VI. Antidepressants ........................................................................................................ Table VII. Others ......................................................................................................................

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377 409 437 449 459 477 485

Foreword The whole is more than the sum of its parts. — Aristotle The sum of all sums is eternity. — Lucretius To say that mass spectrometric analysis of drugs in biological media is similar to archeology may be a bit of a stretch to some, but consider the parallels. The archeologist looks at fragments and sees patterns suggesting whole structures. A pottery shard becomes the intact vessel that in turn reveals cultural aspects of past generations. Likewise, when the forensic toxicologist is presented with a biological specimen, they perform an archeological “dig” for evidence of drug residues. Instead of a shovel or trowel, mass spectrometry becomes the tool for uncovering remains. Pattern analysis of the evidence, a technique used in virtually all fields of scientific endeavor, becomes essential in drug interpretation. Comparisons to standards of known purity are essential. Bodily processes frequently alter pharmaceutical products and illicit drugs to metabolites more suitable for elimination. The “remains” of biological analysis are the analytical report that identifies and provides quantitative information on what was present in the specimen. The first and foremost goal of the analyst is to provide accurate and precise drug identifications and measurements. The power of chromatographic separation coupled with mass spectrometry allows this modern miracle to occur on drug residues that cannot be seen with the naked eye. The analytical report, thus, provides evidence of drug exposure based on what was present and identifiable and how much was present in the specimen. In many cases, the outcome of drug analysis is not a trivial issue and may be used in many circumstances such as guiding therapeutic outcome, accident, death and criminal investigations, and as a requirement in securing or continuing employment. Consequently, the analyst has to get it right! The results must be inconvertible. That is what this book is all about. One of the authors (RHL) and I have discussed the need for documentation of mass spectrometric data on drugs for many years. This work by the authors represents years of work compiling mass spectra of the many forms and derivatives of drugs and their metabolites and their isotopically labeled counterparts. This compilation should well serve those involved in drug analyses of biological specimens and those involved in interpretation of results. Edward J. Cone, Ph.D.

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Preface The analysis of drugs and their metabolites in biological media are now expected to routinely achieve ±20% accuracy in the ng/mL concentration level. This is possible mainly because of the incorporation of the internal standard method, using isotopically labeled analogs of the analytes as the internal standards into the analytical protocols. The availability of various isotopically labeled analogs for a wide variety of drug analytes from commercial sources is also a helpful contributing factor. Using isotopically labeled analogs of the analytes as the internal standards, the most important issue affecting the accuracy of the quantitation results and the achievable linear calibration range is the cross-contribution to the intensities of ions designating the analytes and their isotopically labeled analogs serving as the internal standards. Thus, the availability and the selection of quality ion-pairs designating the analytes and their isotopically labeled analogs (internal standards) are crucial matters. Quality ion-pairs come from careful selections of the isotopically labeled analogs to serve as the internal standards and the derivatization groups for the analyte/internal standard pairs that require chemical derivatization and amenable to chromatography-mass spectrometry methods of analysis. With these understandings in mind, this book is prepared in three parts. Part One of this book includes two descriptive chapters illustrating crucial issues related to quantitative analysis using isotopically labeled analogs as the internal standards in the analytical protocols. Part Two of this book is a systematic compilation of full-scan mass spectra of drugs and their isotopically labeled analogs in various derivatization forms. Part Three of this book is a systematical compilation of crosscontribution data for ion-pairs, derived from various combinations of isotopically labeled analogs and chemical derivation groups that are potentially useful for designating the analytes and their internal standards. One hundred and three drugs along with 134 isotopically labeled analogs included in this study are grouped into 7 categories and accordingly presented in Parts Two and Three. Information included in these three parts should be of routine reference value to individuals and laboratories engaged in the analysis of drugs in biological media. The preparation of this book was conceptualized during the summer of 1990 when one of the authors (RHL) was on an Intergovernmental Personnel Assignment serving as a visiting scientist at the U.S. Addiction Research Center’s Laboratory of Chemistry and Drug Metabolism (Baltimore, Maryland), where Dr. Edward J. Cone then served as the Chief of the Laboratory. A major portion of the laboratory data was collected in 2004 under a contract (DTFAAC-04-C-00012) in the laboratory of Aeromedical Research Division, Civil Aerospace Medical Institute, U.S. Federal Aviation Administration (Oklahoma City, Oklahoma). Additional data collection, data preparation, and writing were completed at Fooyin University (Kaohsiung Hsien, Taiwan) with the support of a 3year (2004–2007) grant from the Taiwanese National Science Council (NSC 93-2745-M-242-003URD, NSC 94-2745-M-242-003-URD, NSC 95-2745-M-242-002-URD). In addition to the financial supports mentioned above, the following colleagues have also made invaluable contributions to the completion of this book project: Chief Toxicologist Dr. Dong-Liang Lin of the Institute of Forensic Medicine (Taipei, Taiwan), Professor Dr. Wei-Tun Chang of Central Police University (Taoyuan Hsien, Taiwan), Principal Scientist Dr. Shiv Kumar of ISOTECTM

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(Miamisburg, Ohio). We are also indebted to the skillful assistance provided by the following undergraduate students from Fooyin University: Meng-Jie Sie (2009), Yu-Shin Lan (2009), ChiungDan Chang (2007), Yi-Chun Chen (2007), and Chia-Ting Wang (2006). Ray H. Liu, Ph.D. Sheng-Meng Wang, Ph.D. Dennis V. Canfield, Ph.D .

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About the Authors Ray H. Liu received a law degree from Central Police University (then Central Police College, Taipei, Taiwan) and a Ph.D. degree in chemistry from Southern Illinois University (Carbondale, IL) in 1976. He is currently a professor in the Department of Medical Technology, Fooyin University (Kaohsiung Hsien, Taiwan), and professor emeritus in the Department of Justice Sciences, University of Alabama at Birmingham. Before pursuing his doctoral training in chemistry, Dr. Liu studied forensic science under the guidance of Professor Robert F. Borkenstein at Indiana University (Bloomington) and received internship training in Dr. Doug Lucas’s laboratory (Centre of Forensic Sciences in Toronto, Canada). Dr. Liu has worked as an assistant professor at the University of Illinois at Chicago, as a chemist at the U.S. Environmental Protection Agency’s Central Regional Laboratory (Chicago, IL), and as a center mass spectrometrist at the U.S. Department of Agriculture’s Eastern Regional Research Center (Philadelphia, PA) and Southern Regional Research Center (New Orleans, LA). He was a faculty member at the University of Alabama at Birmingham for 20 years and retired in 2004 after serving for more than 10 years as the director of the University’s Graduate Program in Forensic Science. Dr. Liu’s works have been mainly in the analytical aspects of drugs of abuse (criminalistics and toxicology), with a significant number of publications in the following subject matters: enantiomeric analysis, quantitation, correlation of immunoassay and GC-MS test results, specimen source differentiation, and development of analytical methodologies. He has authored (or co-authored) several books and book chapters; more than 100 articles in refereed journals; and approximately 150 presentations in scientific meetings. He is qualified by the New York State Department of Health to serve as a laboratory director in forensic toxicology and he has served as a technical director in a U.S. drug-testing laboratory that held major contracts with military, federal, local, and private institutions. Dr. Liu has been an active member of the following professional organizations for more than (or close to) 30 years: the American Chemical Society, Sigma Xi—The Scientific Research Society, the American Academy of Forensic Sciences (fellow), and the American Society for Mass Spectrometry. He is also a member of the Society of Forensic Toxicologists and the American Society of Crime Laboratory Directors (academic affiliate). Dr. Liu consults with several governmental and nongovernmental agencies, including serving as a laboratory inspector for the U.S. and the Taiwanese workplace drug-testing laboratory certification programs. He is the editor-in-chief of Forensic Science Review (www.forensicsciencereview.com) and serves on the editorial boards of the following journals: Journal of Forensic Sciences (1998–2008), Journal of Analytical Toxicology, Journal of Food and Drug Analysis (Taipei), Forensic Toxicology (Tokyo), Forensic Science Journal (Taoyuan, Taiwan), and Fooyin Journal of Health Sciences (Kaohsiung, Taiwan).

Sheng-Meng Wang received a B.S. degree in forensic science from Central Police University (Taoyuan, Taiwan) in 1988 and a Ph.D. degree in chemistry from National Tsing Hua University (Hsingchu, Taiwan) in 1997. Dr. Wang is currently professor of forensic science and director of scientific laboratories, Central Police University. Dr. Wang has been a visiting associate professor at the Graduate Program in Forensic Science, University of Alabama at Birmingham, and conducted research at the U.S. Federal Aviation Administration’s Civil Aerospace Medical Institute (Oklahoma City, OK). Dr. Wang has been working in various areas of forensic toxicology and his current research activities include: evaluation of various chemical derivatization approaches in the sample preparation process, application of xi


solid-phase microextraction to the analysis of drugs in biological fluids, and the characterizations of drug depositions in various biological specimens. Since 1988, Dr. Wang has been serving as a laboratory evaluator for the Drug Testing Laboratory Accreditation Program under the auspices of the (Taiwanese) National Bureau of Controlled Drugs. He has also been serving as the executive secretary for the Taiwan Academy of Forensic Science since 2006.

Dennis V. Canfield received a B.S. degree in biology from Lynchburg College (Lynchburg, VA) in 1971. He completed an M.S. degree in forensic science at John Jay College of Criminal Justice, City University of New York (New York, NY), in 1976. He earned a Ph.D. in forensic chemistry in 1988 at Northeastern University (Boston, MA). For the past 19 years, Dr. Canfield has been the manager of the Bioaeronautical Sciences Research Laboratory at the U.S. Federal Aviation Administration’s Civil Aerospace Medical Institute (CAMI) in Oklahoma City, OK, conducting research into forensic toxicology, biochemistry, radiobiology, functional genomics, and bioinformatics. Before joining CAMI, Dr. Canfield was a senior forensic chemist for the New Jersey State Police Crime Laboratory (Little Falls, NJ) for 5 years and worked as the director of forensic science at the University of Southern Mississippi (Hattiesburg, MS) for 10 years in a tenured associate professor position. Dr. Canfield has worked primarily in the areas of drug identification and toxicology, starting in 1971 at the New Jersey State Police Crime Laboratory, and has continued to the present. He has published numerous peer-reviewed articles on drug identification and toxicology and testified on numerous occasions in federal, state, and local courts as an expert in forensic science. Dr. Canfield has participated as an editor and author in Selected Powder Diffraction Data for Forensic Materials, and Carbon Monoxide and Human Lethality: Fire and Non-Fire Studies. Dr. Canfield is a fellow in the American Academy of Forensic Sciences, a member of the Society of Forensic Toxicologists, Sigma XI Research Society, and the Executive Board of the National Safety Council’s Committee on Alcohol and Other Drugs.

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PART ONE ISOTOPICALLY LABELED ANALOG AS INTERNAL STANDARD FOR DRUG QUANTITATION — METHODOLOGY


3

Chapter 1 Quantitation of Drug in Biological Specimen — Isotopically Labeled Analog of the Analyte as Internal Standard — INTRODUCTION ....................................................................................................................... 3 Significance of Accurate Quantitation ........................................................................................ 3 Preferred Calibration Method ..................................................................................................... 4 I. INTERNAL STANDARD AND QUANTITATION IONS ...................................................... 4 A. Inadequate Isotopic Purity — An Extrinsic Factor .............................................................. 4 B. Cross-Contribution Derived from Ion Fragmentation Mechanism — An Intrinsic Factor ................................................................................................................ 5 II. FITTING CALIBRATION DATA ............................................................................................. 6 III. 2H- VERSUS 13C-ANALOGS AS INTERNAL STANDARDS ............................................... 7 CONCLUDING REMARKS ...................................................................................................... 9 REFERENCES .......................................................................................................................... 10

INTRODUCTION The detection of drugs and their metabolites (collectively referred to as drugs hereafter) in biological tissues and fluids (collectively referred to as biological media hereafter) has always been an important component in clinical diagnostic analysis, forensic testing, pharmacological research, and drug discovery study. With advances in analytical instrumentation and a greater understanding of metabolism, we can now analyze drugs at a much lower concentration that was previously undetectable. Recent emphasis on monitoring illegal drug use in the workplace calls for massive testing of urine specimens, which has inspired the development and significant advances in specimen pretreatment technologies. Newer instrumentation, such as GC-MS/MS or LCMS/MS, capable of providing greater specificity and signal-to-noise ratio, are advantageous for identifying unknown metabolites at low concentrations. On the other hand, robust GC-MS methods are routinely used under therapeutic drug monitoring, emergency room drug screening, and workplace drug testing settings, in which the drugs of interest have previously been well characterized and often present at higher levels. Analytical instrumentation and specimen pretreatment technologies are “hardware” aspects of the analytical sciences; the development and implementation of comple-

mentary “software” components help reach the full potential made possible by hardware advances. For example, the development of the “internal standard” method [1,2], especially the adaptation of isotopically labeled analogs (ILAs) as the internal standards (ISs) [3,4], has greatly improved the accuracy in the quantitation of drugs in biological media. Developments related to the use of ILAs as the ISs for accurate quantitation are based on GCMS technology and readily adapted into GC-MS/MS, LC-MS, and LC-MS/MS applications. While many GCMS/MS, LC-MS, and LC-MS/MS studies utilize ILAs as ISs, they do not generate better quantitative results than GC-MS and we know none that was devoted to better understanding the methodology itself. Significance of Accurate Quantitation Recent government regulations in workplace drug testing activities include monitoring quantitative data [5]; thus, making quantitation an important aspect of quality control practices in the analysis of drugs in biological media. Furthermore, specific “cutoff” value has been adapted as one of the essential criteria for defining whether a specific test specimen is “positive” or “negative” for a targeted drug. Accurate quantitation has now become an essential part of the routine testing protocol; it has, in addition to being a scientific pursuit, evolved into a legal issue.

Chapter 1 — Isotopically Labeled Analog as Internal Standard © 2010 by Taylor and Francis Group, LLC

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In many non-routine analytical settings, emphasis may be placed on the detection of a drug at very low concentrations and interpretation of quantitative data with small inter-specimen drug concentration differences. Furthermore, sample preparation approaches often result in a final aliquot with hundred- or thousand-folds concentration in drugs’ content; raw analytical result derived from the measurement step are then multiplied by a factor (of two or three orders of magnitude), thereby grossly magnifying any inaccuracies embedded in the raw data. Thus, proper interpretation and utilization of analytical findings rely heavily on the accuracy of the raw analytical data. This is especially critical in circumstances where drugs are present at a very low concentration level and interpretations are based on small inter-specimen differences, e.g., in hair-related studies where the objectives are on: a. Differentiating drugs derived from external contamination from incorporation through active ingestion [6]; b. Determining racial bias due to the drug incorporation process or drug recovery in the sample pretreatment step [7]; or c. Assessing variation in susceptibility to environmental contaminations due to differences in race origin [8] or hair treatments [9].

standards and test specimens are spiked with the same amount of the IS. Quantitation is achieved by comparing a selected drug-to-IS ion-pair intensity ratio observed in the test specimen with the same ratio observed in the calibration standard(s). With practically identical chemical property and mass spectrometric fragmentation characteristics, an ILA is a preferred IS because it offers the following advantages: a. Errors derived from (i) incomplete recovery of the drug in the sample preparation process or (ii) varying gas chromatographic and mass spectrometric conditions are compensated for; and b. The presence of interfering materials (or mechanisms) affecting the detection (or quantitation) of the drug will result in the absence of the IS in the final chromatogram [10] or altered response and ion intensity ratios [11]; thus, alerting the analyst to conduct further investigation.

I. INTERNAL STANDARD AND QUANTITATION IONS Under low resolution measurement conditions, the intensities of ions designating the drug and the IS are representative of these compounds’ concentrations only if the following conditions are met:

Preferred Calibration Method Accurate quantitation requires a proper calibration (standardization) procedure to fully account for artifacts derived from variations in specimen matrix, specimen preparation, and instrumental conditions. Three most commonly used calibration techniques are the analytical or working curve, standard additions, and internal standard methods [1,2]. Mass spectrometric methods have proven to be one of the most sensitive and specific methods for drug assay. In particular, selected ion monitoring (SIM) approach has been used for several decades to achieve better accuracy and precision in ion intensity measurements. This approach is still an integral part of the quantitation protocol involving various forms of mass spectrometric methods in where an internal standard method is used. A typical protocol involves monitoring several selected corresponding ions (referred to as "ion-pairs" hereafter) designating the targeted drug and the ILA adapted as the IS. One or several calibration standards, containing known amounts of the drug, are processed in parallel with test specimens throughout the entire analytical protocol. All calibration

a. The ILA is isotopically pure (an extrinsic factor); and b. An adequate number of the labeling isotopes are positioned at appropriate locations in the molecular framework, so that, after the fragmentation process, ions meeting the following requirements are present (an intrinsic factor): (i) with high-mass and significant intensities; (ii) retaining at least three labeling isotopes; and (iii) without (or with insignificant) cross-contribution or CC (see Section II in Chapter 2 for full description on this phenomenon) between the ions designating the drug and the IS.

A. Inadequate Isotopic Purity — An Extrinsic Factor If the ILA is not manufactured with sufficient isotopic purity, the addition of the IS, especially when a high concentration of the ILA is used, will result in the observation of a significant amount of the drug in a truly negative specimen. For a truly positive specimen, the resulting quantitative data will include systematic errors. This problem has been well illustrated by a benzoylecgonine (BZ) study [12] in which a high concentration of ILA IS (1,500 ng/mL BZ-d3) was adapted.

Isotopically Labeled Analog as Internal Standard for Drug Quantitation — Methodology © 2010 by Taylor and Francis Group, LLC

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At the time of the study, a high concentration of IS (BZd3) was commonly used by laboratories engaged in testing workplace specimens. Since the concentration of BZ encountered in positive samples are typically high (>5,000 ng/mL), adapting a high IS concentration can minimize the following problems: a. To reduce the intensities of the ions designating the analyte (BZ), solvent volume used to reconstitute the extract may be so large that the resulting IS become too dilute to generate adequate ion intensity for reliable quantitative determination; and b. The contribution of the isotopic ions, derived from the naturally abundant 13C-atoms in the analyte, to the intensity of ions designating the IS may become very significant when the concentration of the latter is disproportionally low.

This study [12] examined two lots of 0.1 mg/mL BZd3 in methanol. With the addition of 4.5 μg BZ-d3 IS into 3 mL of urine samples (corresponding to 1,500 ng/mL), followed by solid-phase extraction, derivatization, and concentration down to 100 μL for GC/MS analysis, ions designating BZ (m/z 331, 272, and 210) were observed in truly negative test specimens. For a negative specimen, the concentration (X) of the observed BZ caused by the addition of these two lots of IS were 7.080 and 28.99 ng/ mL as calculated by Equation 1-1. X / (1,500 – X) = (Ion intensity of m/z 210) / (Ion intensity of m/z 213)

(1-1)

(where ions m/z 210 and 213 were used to designate BZ and the IS.) These concentrations correspond to 0.472% and 1.87% impurity of BZ in these two lots of BZ-d3 IS provided by that specific manufacturer in 1988. Isotopically impure ISs also introduced systematic errors embedded in the quantitative data derived from positive specimens. Data shown in Table 1-1 demonstrate the systematic errors exhibiting the following characteristics: a. No error is introduced if the concentration of the BZ in the test specimen is at the exact level of the BZ in the calibration standard. b. A higher apparent result will be observed if the concentration of the BZ in the test specimen is lower than the concentration of the BZ in the calibration standard, and vice versa. c. The degree of the above deviations increases as the isotopic impurity in the adapted IS increases.

Table 1-1. Quantitation error as a function of the isotopic impurity level of the internal standard and the difference between the analyte concentration in the calibration standard and the test sample Isotopic impuritya,b

7.080

27.99

Apparent concentrationa,c

True concentrationa,c

% Error

83.82 141.1 146.0 147.1 147.3 148.1 252.1

80.70 140.7 145.7 147.0 147.2 148.0 256.9

+3.87 +0.284 +0.206 +0.0680 +0.0679 +0.0676 –1.87

84.19 154.1 155.5 156.8 161.7 273.5 288.9 292.5 293.9 298.3

72.28 154.8 156.6 158.0 163.9 296.6 314.6 319.1 320.7 326.0

+16.5 –0.453 –0.702 –0.759 –1.34 –7.79 –8.17 –8.34 –8.36 –8.50

a Concentration in ng/mL. The concentration of the IS is 1,500 ng/ mL. The analyte’s (benzoylecgonine) concentration in the calibration standard is 150 ng/mL. b 7.080 and 27.99 ng/mL of benzoylecgonine are included in the 1,500 ng/mL of benzoylecgonine-d3 IS. c See the original reference [12] for the calculation of the apparent and true analyte concentrations.

B. Cross-Contribution Derived from Ion Fragmentation Mechanism — An Intrinsic Factor Under typical GC-MS analytical conditions, the drug and the IS are chromatographically inadequately resolved; thus, a proposed ILA IS must generate at least one (preferably two or three) ions relatively free from CC by the drug. There must also be at least one ion designating the drug that is relatively free from CC by the proposed ILA IS. (Current practice requires at least three “interference-free” ions derived from the drug allowing monitoring two ion-intensity ratios as an important criterion for drug confirmation.) To make this possible, the labeling isotopes in the ILA must be positioned at appropriate locations in the molecular framework, allowing the fragmentation process to generate a sufficient number of high-mass ions (with significant intensities) that (a) retain the labeling isotopes; and (b) will not interfere with the intensity measurement of ions derived from the drug. Otherwise, the [M + n] ion (derived from the drug) may, because of the naturally occurring isotope abundance, make a significant contribu-


6

II. FITTING CALIBRATION DATA Series of ions, [M – Hn], are typically seen in the EI fragmentation process [14,15]. The [M – Hn] processes, the presence of the naturally abundant 2H-atoms in the drug and the 1H-atoms in the 2H-labeled IS, the isotopic effect of the [M – Hn] processes [16,17], and varying conditions in each sample (test specimen or standard) prohibit quantitations based on direct comparison of intensities of ions derived from the drug and the corresponding ion of the IS. The effects of these phenomena are minimized by comparing the drug/ILA IS ion-pair intensity ratio observed in the test sample against those observed in one or a set of calibration standards.

35

a: m/z 196/200 b: m/z 181/185

30

Analyte/IS ion intensity ratio

tion to the intensity of the ion designating the ILA that corresponds to the [M] ion of the drug. (“M” is the mass of the ion derived from the drug and selected for monitoring; “n” is the nominal mass difference of the ions designating the drug and the ILA serving as the IS.) If deuterium, as in most currently available commercial products, is used as the labeling isotope, a difference in three mass units (n = 3) between the drug and the ILA is sufficient under normal circumstances. (If the concentration of the analyte is disproportionally higher than the concentration of the IS included in the assay process, the intensity of the [M + 3] ion originated from the analyte may become significant enough to require an additional analysis using a diluted aliquot.) Secobarbital/13C4-secobarbital (SB/13C4-SB) data shown in Figure 1-1 [13] illustrate how CC (of the intensities of ions designating SB and the IS) affects the accuracy in quantitation. In this example, CCs between the first pair of ions (m/z 196/200) are so insignificant (see CC data shown in the legend of the figure) that the linearity of the “SB/IS ion-pair intensity ratio” versus “SB concentration” plot (Figure 1-1-a) extends through a wide analyte concentration range. On the other hand, CCs between the two ions in the second ion-pair (m/z 181/185) are much more significant. In this latter case, significant errors can occur if the ion-pair intensity ratio generated from the test specimen is used directly to determine the analyte’s concentration using a linear calibration model. The error can become very serious if the drug’s concentration in the test specimen is significantly higher or lower (Figure 1-1-b) than the drug concentration adapted in the calibration standard (see further discussion in the next section — Fitting Calibration Data).

a

25 20

b 15 10 5 0 0

1000

2000

3000

5000

Figure 1-1. Fitting calibration data adapting linear (a) and hyperbolic (b) models using ion-pairs with different degrees of cross-contribution from the secobarbital/secobarbital-13C4 system. (a) m/z 196/200: 0.23% of the measured intensity of m/z 196 (designating secobarbital) is contributed by secobarbital13C ; while 0.017% of the measured intensity of m/z 200 4 (designating secobarbital-13C4) is contributed by secobarbital. (b) m/z 181/185: 1.6% of the measured intensity of m/z 181 (designating secobarbital) is contributed by secobarbital-13C4, while 0.29% of the measured intensity of m/z 185 (designating secobarbital-13C4) is contributed by secobarbital [13].

A typical quantitative GC-MS protocol usually involves monitoring several selected ions from the drug and the ILA IS. Quantitation is achieved by comparing a selected drug-to-ILA ion-pair intensity ratio observed from the test sample against the same ratio observed from the calibration standard. The calibration standard contains the same amount of the IS (as those added to the test specimens) and a known amount of the drug, and is processed in parallel with the test specimens. The drug’s concentration in the test specimen can be calculated using a onepoint calibration approach as shown Equation 1-2. The one-point calibration approach, in fact, is a twopoint linear calibration method using only one empirical data point with the assumption that: a. The drug-to-ILA ion-pair intensity ratio is zero when the drug’s concentration in the test specimens or the standards is zero, i.e., the ILA IS will not contribute to the intensity of the ion monitored for the drug; and b. The drug-to-ILA ion-pair intensity ratio will truly reflect the drug/ILA IS concentration ratio in the test specimens (and the standards), i.e., the drug will not contribute to the intensity of the ion monitored for the IS, and vice versa.


4000

Analyte concentration (ng/mL)

7

[Int. of ion designating the analyte) / (Int. of ion designating IS)]

Test specimen

[Int. of ion designating the analyte) / (Int. of ion designating IS)]

Cal. standard

In fact, these two assumptions are rarely valid for two reasons: a. The ILA IS often contains a small amount of isotopic impurity, i.e., the drug; and b. Ion fragmentation mechanisms often result in CC of the intensities of ions designating the drug and the IS.

Thus, drug concentrations derived from one-point calibration often include systematic errors as shown in Table 1-1 [12] and Figure 1-1-b (the m/z 181/185 ion-pair plot) [13]. The error is absent when the drug’s concentration in the test specimen is the same as that in the calibration standard, but systematically increases as the drug’s concentration in the test specimen is increasingly differently from that in the calibration standard. Multiple-point linear calibration approaches, in which the observed drug-to-ILA IS ion-pair intensity ratios are plotted against the drug’s concentration, are commonly used to extend quantitation to a wider concentration range. However, systematic errors still exist due to the inherently non-linear nature of the calibration curve. Basically, both of the abovementioned one-point and multiple-point approaches are based on linear models; thus, similar errors will be observed as long as the assumptions for the linear model are violated. For calibration purposes, a “linear with zero intercept” relationship between the measured response and the drug’s concentration is preferred. Thus, logarithmic-transformed ion-pair intensity ratio was proposed [18] to establish the standard curve, which was reportedly linear with an upper concentration of BZ up to 500,000 ng/mL. Theoretical considerations [19] and various correction approaches [20–22] addressing the CC phenomenon have been reported. Our studies [23] have demonstrated that the hyperbolic model works well in cases where calibration data are derived from ion-pairs with significant CCs. This is clearly demonstrated in Figure 1-1-b (the m/z 181/185 ion-pair plot). The effectiveness of the hyperbolic model is a result of its taking into account the CC phenomenon as shown in Equation 1-3 [24]. y = (xX + aA') / (xX' + aA); (x + aA'/X) / (xX'/X + aA/X); or (x + C1) / (C2 x + C3)

(1-3)

× (Analyte concentration) Cal. standard

where y = the observed ion-pair intensity ratio; x = moles of the analyte in each standard; X = intensity of the ion designating the analyte (generated by analyte); a = moles of the IS in all standards; A' = IS’s cross-contribution to the the intensity of the ion designating the analyte; X' = analyte’s cross-contribution to the intensity of the ion designating the IS; and A = intensity of the ion designating the IS (generated by IS).

Constant C1 expresses the CC of the IS to the intensity of ion designating the drug; constant C2 expresses the CC of the drug to the intensity of ion designating the IS; while constant C3 reflects the moles of the IS used, the relative purity of the drug and the IS used in preparing the standard solutions, and the relative intensities of the ions designating the same amount of the drug and the IS. Constant C3 equals the concentration of the IS when both the drug and the IS are 100% pure (chemically and isotopically) with identical mass spectral responses (no isotopic effect). In the absence of CC between the drug and the IS, C1 = C2 = 0; thus, the relationship between the drug/IS ion intensity and concentration ratios reduces to a linear function (Equation 1-4). y = Cx

(1-4)

where C = 1/C3. III. 2H- VERSUS 13C-ANALOGS AS INTERNAL STANDARDS While evaluating the effectiveness of the 13C4- and 5-analogs of SB [25] and butalbital (BB) [26] in serving as the ISs, we have observed an interference phenomenon in cases where 2H5-analogs of these two barbiturates were adapted. Specifically, the intensity ratios of the ion-pairs designating these two drugs and their respective 2H5analogs increase as the volume of the solvent (ethyl acetate) used to reconstitute the extraction/derivatization residue increases. This phenomenon was not observed when the respective 13C4-analogs were used as the ISs in parallel experiments. Since this interference phenomenon was observed only in the 2H-labeled, but not in the 13C-labeled systems, we do not believe the reported self-chemical ionization 2H


(1-2)

8

phenomenon [27,28] is the underlying cause. Since the 2H-atoms in the SB-d and BB-d are placed at allylic posi5 5 tions, it was hypothesized that hydrogen/deuterium exchange has taken place at the ion source. This hypothesis was disproved [29] by the observation of the same phenomenon for drug/2H-analog pairs with (such as SB, BB, and methohexital) and without (such as PB, and phenobarbital) this structural feature (Figure 1-2, Table 1-2). Drug/13C4-analog systems differ from the corresponding drug/2H5-analog systems in displaying an identical retention time for the drugs and the ILA ISs. Thus, retention time difference between the drug and the 2H-analog IS was hypothesized as the underlying factor causing the increase in the ion-pair intensity ratio observed for the drug/2H-analog systems (but not for the drug/13C-analog systems). To test this hypothesis, several series of experiments were performed, in which GC column temperature programming conditions were varied to modify the separation between the drug and the 2H-analog IS [29]. The resulting drug-to-IS ion-pair intensity-ratio changes were characterized and evaluated. SB/SB-13C4 system was again used as the control, the monitored ion-pair intensity ratio for this system remains constant as the reconstitution volume is increased and the temperature programming rate was changed from 30 to 15, and then to 5 oC/min. This was consistent with the hypothesis because the retention times for the drug and the 13C-analog IS remain the same (no separation) regardless of the programming rate. Data resulting from a series of parallel experiments for the SB/SB-d5 system are shown in Table 1-3. Here, as the programming rate was reduced from 30 to 15, and then to 5 oC/min, the separation between the drug and the 2Hanalog IS increased, with the percentage of m/z 196 overlapped (by m/z 201) reducing from 89.5 to 77.7, and then to 70.2%. Under these three temperature-programming conditions and when the reconstitution volume was changed from 20 to 200 μL, the monitored ion-pair inten-

CH 3

O

N

O

CH(CH 3)C3 H7

N H3 C

O

N

H3C

O

O

H 3C

O

CH2CH= CH2

N

(b-1)

O

CH3

O

O

CD2CD=CD2

H 3C

*

O

N

O

(c-2) CH3

CH3 N

O

O CH(CH3)C3H 7 C 2H 5

N

H 3C

O

N

2

O

(d-2)

CH3 N

CH3 O C 6 H5 C 2 H5

N

H 3C

O CH(CH3)C3 H7 C D5

N H 3C

(d-1) O

O CH(CH 3 )C≡ CC H 2 5 CD2CD=CD 2

N

H 3C

(c-1) O

CH2CH=CH 2

: 13C

CH3 O

O CH(CH 3 )C≡ CC 2H5 CH2 CH=CH2

N

H3 C

O

* : 13C

CH2CH(CH3)CH3

(b-3)

CH3

N

O

N * * N * *

(b-2) O

CH2CH= CH2

(a-* 3)

CH2CH(CH3)CH3

N H3C

* : 13C

CH(CH3)C3H7

: 13C

CH3

O

O CH2CH(CH3)CH3

N H3C

CD2CD=CD2

O

N

* * N * *

(a-2)

CH3

N

O

O CH(CH 3)C 3H7

N

CH CH = CH 2 2

(a-1) O

CH 3

CH3

O

O

(e-1)

O

N

C6H5 C2D5

N

H 3C

O

O

(e-2)

Figure 1-2. Structures of analytes/isotopically labeled analogs (all as methyl-derivatives): secobarbital/secobarbital-d5/ secobarbital-13C4 (a); butalbital/butalbital-d5/butalbital-13C4 (b); methohexital/methohexital-d5 (c); pentobarbital/pentobarbitald5 (d); phenobarbital/phenobarbital-d5 (e).

sity ratio for the SB/SB-d5 system changed 11.92%, 15.71%, and 18.35%, respectively. Another series of experiments for the SB/SB-d5 system were performed, in which the 2H-analogous IS, rather than the drug, was the major component. In this latter case, as the programming rate was reduced from 30 to 15, and then to 5 oC/min, the separation between the drug and the IS similarly increases, with the percentage

Table 1-2. Analyte/isotopic analog ion-pair intensity ratio as a function of molecular abundance— Analyte: 2,500 ng/mL; isotopically labeled analog: 400 ng/mL Reconstitute volume (μL) 10 30 60 100 150

Butalbital (196/201) 5.429 6.697 6.790 7.134 7.132

Analyte/2H5-analog (m/z) Secobarbital Methohexital Pentobarbital Phenobarbital (196/201) (261/266) (184/189) (232/237) 5.997 7.167 7.435 7.644 7.703

8.814 9.110 9.715 10.56 10.84

11.87 12.58 12.93 13.34 13.44

6.831 7.726 7.878 7.878 7.955

Analyte/13C4-analog (m/z) Butalbital Secobarbital (196/200) (196/200) 7.586 7.548 7.549 7.547 7.518


7.018 7.051 7.022 6.926 6.867

9

Table 1-3. Secobarbital/secobarbital-d5 (SB/SB-d5) ion-pair intensity ratio (m/z 196/201) as a function of molecular abundance under three temperature programming conditions resulting in different peak overlapping between SB and SB-d5 — SB: 4,800 ng/mL; SB-d5: 400 ng/mL Rec. vol. (μL) 20 30 40 60 80 120 160 200

30 oC/min temperature ramp Ion int. Ratio Overlapa ratio change (%) (%) 10.49 10.69 11.03 10.99 11.41 11.39 11.62 11.74

Average

1.91 5.15 4.77 8.77 8.58 10.77 11.92

—b 97.3 — 83.4 — 89.6 — 87.6

15 oC/min temperature ramp Ion int. Ratio Overlapa ratiochange (%) (%) 10.82 11.32 11.67 11.90 11.89 12.35 12.38 12.52

89.5

4.62 7.86 9.98 9.89 14.14 14.42 15.71

— 80.5 — 78.0 — 79.1 — 73.2

5 oC/min temperature ramp Ion int. Ratio Overlapa ratio change (%) (%) 11.50 11.89 12.35 12.50 12.87 12.99 13.36 13.61

77.7

3.39 7.39 8.70 11.91 12.96 16.17 18.35

— 70.0 — 71.8 — 73.2 — 66.0 70.2

a Percentage of overlaps are calculated by dividing the area of m/z 196 that is overlapped with m/z 201 by the total peak area of m/z 196. Percentages of overlap with 30, 15, and 5 oC/min temperature ramps are approximately 89.5 ([97.3 + 83.4 + 89.6 + 87.6]/4), 77.7 ([80.5 + 78.0 + 79.1 + 73.2]/4), and 70.2 ([70.0 + 71.7 + 73.2 + 66.0]/4), respectively. Area calculations were done by rectangular summation method [30]. b Data not calculated.

of m/z 201 overlapped (by m/z 196) reducing from 100 to 94.3, and then to 62.4%. Under these three temperature programming conditions and when the reconstitution volume was changed from 20 to 200 μL, the monitored ion-pair intensity ratio for the SB/SB-d5 system changed –7.65%, –14.2%, and –23.2%, respectively. The phenomena observed from these three series of experiments are rationalized as follows: • When two chromatographically closely-eluted compounds (such as drug/2H-analog pairs) with their overlapping portions appearing at the ion source at the same time, the non-overlapping portions will have a higher ionization efficiency; thus, over-all ionization efficiency of the major component will be lower than that of the minor one. • This difference in ionization efficiency between the major and the minor compounds becomes more significant when the total molecular population at the ion source is higher, i.e., with smaller reconstitution volume. This explains why, as the reconstitution volume is increased from 20 to 200 μL, the monitored ion-pair intensity ratios increase in Table 1-3 (SB as the major component), while decrease when SB-d5 is the major component. • As the drug and the 2H-analog IS are more closely eluted, larger portions of these two compounds will appear at the ion source at the same time. Since these portions are proportionally affected by the decrease in their ionization efficiencies, the difference in the overall ionization efficiency of these two compounds will decreases as they are more closely eluted. This explains why the rate of the changes (as the reconstitution volume is increased from 20 to 200 μL) in the monitored ion-

pair intensity ratio is much higher when the temperatureprogramming rate is decreased (drug and IS are better resolved).

The above reasonings are consistent with the observed peak overlapping data and ion-pair intensity ratio change characteristics shown in Table 1-3. They may also account for the reported interference on the quantitation of BZ caused by the coelution of fluconazole [11]. The authors attributed the observed “coeluting interference” to “saturation of the ionization chamber”, but did not mention non-proportional variations in BZ/BZ-d5 ionization efficiencies. CONCLUDING REMARKS Since the now well-known ion CC phenomenon exists in most (if not all) drug/ILA IS systems, calibration curves generated from these systems are likely nonlinear. In systems where ion CC is absent, calibration curves generated from a drug/2H-analog system is still inherently non-linear. This is due to the fact that the intensity ratio of an ion-pair (designating the drug/2Hanalog in a specific sample with the same concentration ratio) varies as their molecular abundances in the mass spectrometer ion source are changed. Variations can result from injecting different volume or injecting the same volume of a drug/2H-analog mixture with different concentration but the same ratio. The non-linear characteristics of the calibration curve are also affected by the separation between the drug and its 2H-analog IS,


10

which is affected by the number and position of the 2Hatoms placed in the molecular framework (an intrinsic factor) and the column temperature programming condition (an extrinsic factor). Thus, for most accurate quantitations, non-linear approaches [23] should be seriously considered for establishing the calibration curve. REFERENCES 1. Willard HH, Merritt LL Jr, Dean JA, Settle A Jr: Instrumental Methods of Analysis, 7th ed; Wadsworth Publishing: Belmont, CA, p. 32; 1988. 2. Krull I, Swartz M: Quantitation in method validation; LC•GC 16:1984; 1998. 3. De Leenheer AP, Lefevere MF, Lambert WE, Colinet ES: Isotope-dilution mass spectrometry in clinical chemistry; Advances in Clinical Chemistry, Vol 24; Academic Press: London, UK; pp 111–161; 1985. 4. Garland WA, Barbalas MP: Applications to analytical chemistry: an evaluation of stable isotopes in mass spectral drug assays; J Clin Pharmacol 26:412; 1986. 5. U.S. Department of Health and Human Services (Substance Abuse and Mental Health Services Administration): Mandatory guidelines for federal workplace drug testing programs; Fed Reg 73:71858; 2008. 6. Blank DL, Kidwell DA: Decontamination procedures for drugs of abuse in hair: are they sufficient? Forensic Sci Int 70:13; 1995. 7. Mieczkowski T, Newel R: An evaluation of racial bias in hair assays for cocaine: black and white arrestees compared; Forensic Sci Int 63:85; 1993. 8. Sellers JK: The Effects of Hair Treatment on Cocaine Contamination from External Exposure — Master’s thesis; Univ. of Alabama at Birmingham: Birmingham, AL, 1994. 9. Cirimele V, Kintz P, Mangin P: Drug concentration in human hair after bleaching; J Anal Toxicol 19:331; 1995. 10. Brunk SD: False negative GC-MS assay for carboxy THC due to ibuprofen interference; J Anal Toxicol 12:290; 1988. 11. Wu AH, Ostheimer D, Cremese M, Forte E, Hill D: Characterization of drug interferences caused by coelution of substances in GC-MS confirmation of targeted drugs in full-scan and selected ion monitoring modes; Clin Chem 40:216; 1994. 12. Liu RH, Baugh LD, Allen EE, Salud SC, Fentress JG, Ghadha H, Walia AS: Isotopic analogue as the internal standard for quantitative determination of benzoylecgonine: concerns with isotopic purity and concentration level; J Forensic Sci 34:986; 1989. 13. Liu RH, Lin T-L, Chang W-T, Liu C, Tsay W-I, Li J-H, Kuo T-L: Isotopically labeled analogues for drug quantitation; Anal Chem 74:618A; 2002. 14. Peterson DW, Hayes JM: In Hercules DM, Hieftje GM, Snyder LR, Evenson MA (Eds): Contemporary Topics in Analytical and Clinical Chemistry, Vol 3; Plenium Press: New York; pp. 217–252; 1978.

15. MacCoss MJ, Toth MJ, Matthews DE: Evaluation and optimization of ion-current ratio measurements by selected-ion-monitoring mass spectrometry; Anal Chem 73:2976; 2001. 16. Low IA, Liu RH, Barker SA, Fish F, Settine RL, Piotrowski EG, Damert WC, Liu J-Y: Selected ion monitoring mass spectrometry: parameters affecting quantitative determination; Biomed Mass Spectrom 12:633; 1985. 17. Benz W: Accuracy of isotopic label calculations for spectra with a (molecular ion – hydrogen) peak; Anal Chem 52:248; 1980. 18. Corburt MR, Koves EM: Gas chromatography/mass spectrometry for the determination of cocaine and benzoylecgonine over a wide concentration range (10% CC or with 5% (based on SIM data) are also excluded from the table. Common practices in choosing the linear model for calibration mandate the use of ion-pairs with low CC for quantitation (or as a criterion for qualitative confirmation purpose). This is especially true when the calibration is to be established for a reasonable concentration range (e.g., in three orders of magnitude), as demonstrated in an earlier study [14]. An ion-pair with significant CC can be noted by the presence of the cross-contributing ion in the full-scan mass spectrum of the corresponding isotopic analog. The CC data may appear to be irrelevant in cases where the number of the isotopic atoms in the ILAs is so large that the analytes and the ISs are practically resolved chromatographically. However, these analogs (such as methamphetamine-d14) are still included in this study for the following two reasons: (a) to optimize the analytical time and to keep the system clean, chromatography is normally conducted at high temperatures resulting in inadequate resolution between the analyte and the IS; and (b) the retention time window set for automatic integration of ion intensities may not always be properly adjusted.

Chapter 2 — Chemical Derivatization and Mass Spectrometric Data Collection © 2010 by Taylor and Francis Group, LLC

28

The sequence and manner adapted to present CC data are different from that adapted for presenting the full-scan mass spectra in Appendix One. Specifically, CC data are presented in table format and the CC data for all chemical derivatization products for one specific isotopic analog are included in one table. For example, with six ILAs included in this project, amphetamine’s CC data are presented in six tables, ranging from Table I-1a to Table I-1f (pp 381–388), where “I” is the designation of compound category, stimulant; “1” is the designation of the first compound in this category, amphetamine; and “a” to “f” are the designations of the six isotopically labeled analogs). These six tables summarize the CC data for the following analyte/ILA pairings: amphetamine/amphetamine-d5 (Table I-1a), amphetamine/amphetamine-d5(ring) (Table I-1b), amphetamine/amphetamine-d 6 (Table I-1c), amphetamine/amphetamine-d8 (Table I-1e), amphetamine/amphetamine-d10 (Table I-1e), and amphetamine/ amphetamine-d11 (Table I-1f). Similarly, methamphetamine's CC data are presented in Table I-2a to Table I-12e (pp 388–393). Each table includes all derivatization groups that have been attempted. The order of appearance of these derivatization groups in each table is the same as those listed in Table 2-2 in this chapter. CONCLUDING REMARKS Following a review on: (a) the structural features of commonly encountered drugs; (b) commercially available isotopically labeled analogs of these drugs; and (c) commonly utilized chemical derivatization approaches, the authors have carried out a series of chemical derivatization experiments and collected a set of full-scan mass spectra and CC data for ion-pairs with potential for designating the analytes and their ILAs serving as the ISs. An approach for evaluating the accuracy of a set of specific CC data has been presented; however, the CC data summarized in Appendix Two have not been systematic validated. Full-scan mass spectra compiled in Appendix One represent the most comprehensive collection of mass spectra for these drugs and their isotopic analogs in various chemical derivatization forms. Comprehensive listings of CC data shown in Appendix Two should save an enormous amount of time and efforts for practicing laboratories in their search for this analytical parameter to establish optimal quantitation protocols.

REFERENCES 1. SOFT/AAFS Forensic Toxicology Laboratory Guidelines (2006 Version); Section 8 (www.soft-tox.org). 2. Liu RH, Lin T-L, Chang W-T, Liu C, Tsay W-I, Li J-H, Kuo T-L: Isotopically labeled analogues for drug quantitation; Anal Chem 74:618A; 2002. 3. Lin DL, Chang WT, Kuo TL, Liu RH: Chemical derivatization and the selection of deuterated internal standard for quantitative determination — Methamphetamine example; J Anal Toxicol 24:275; 2000. 4. Lin DL, Wang SM, Liu RH: Chemical derivatization in drug analysis — A conceptual review; J Food Drug Anal 16:1; 2008. 5. Smith FP, Kidwell D: Commentary on minimal standards for the performance and interpretation of toxicology tests in legal proceedings; J Forensic Sci 45:237; 2000. 6. Chang WT, Lin DL, Low IA, Liu RH: 13C4-Secobarbital as the internal standard for the quantitative determination of secobarbital — A critical evaluation; J Forensic Sci 45:659; 2000. 7. Chang WT, Liu RH: Mechanistic studies on the use of 2Hand 13C-analogs as internal standards in selected ion monitoring GC-MS quantitative determination — Butalbital example; J Anal Toxicol 25:659; 2001. 8. Chang WT, Lin DL, Liu RH: Isotopic analogs as internal standards for quantitative analyses by GC/MS — Evaluation of cross-contribution to ions designated for the analyte and the isotopic internal standard; Forensic Sci Int 121:174; 2001. 9. Valtier S, Cody JT: Evaluation of internal standards for the analysis of amphetamine and methamphetamine; J Anal Toxicol 19:375; 1995. 10. Urry FM, Kushnir M, Nelson G, McDowell M, Jennison T: Improving ion mass ratio performance at low concentration in methamphetamine GC-MS assay through internal standard selection; J Anal Toxicol 20:592; 1996. 11. Wu C-H, Huang M-H, Wang S-M, Lin C-C, Liu RH: Gas chromatography-mass spectrometry analysis of ketamine and its metabolites — A comparative study on the utilization of different derivatization groups; J Chromatogr A 1157:336; 2007. 12. Wu C-H, Yang S-C, Wang Y-S, Chen B-G, Lin C-C, Liu RH: Evaluation of various derivatization approaches for gas chromatography-mass spectrometry analysis of buprenorphine and norbuprenorphine; J Chromatogr A 1182:93; 2008. 13. Liu RH, Foster G, Cone EJ, Kumar SD: Selecting an appropriate isotopic internal standard for gas chromatography/mass spectrometry analysis of drugs of abuse — Pentobarbital example; J Forensic Sci 40:983; 1995. 14. Whiting TC, Liu RH, Chang W-T, Bodapati MR: Isotopic analogs as internal standards for quantitative analyses of drugs/metabolites by GC/MS — Non-linear calibration approaches; J Anal Toxicol 25:179; 2001.


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15. Chen B-G, Wang S-M, Liu RH: GC-MS analysis of multiply-derivatized opioids in urine; J Mass Spectrom 42:1012; 2007. 16. Szirmai M, Beck O, Stephansson N, Halldin MM: A GCMS study of three major acidic metabolites of delta-1tetrahydrocannabinol; J Anal Toxicol 20:573; 1996. 17. Huang W, Moody DE, Andrenyak DM, Smith EK, Foltz RL, Huestis MA, Newton JF: Simultaneous determination of delta-9-tetrahydrocannabinol and 11-nor-9-carboxydelta-9-tetrahydrocannabinol in human plasma by solidphase extraction and gas chromatography-negative ion chemical ionization-mass spectrometry; J Anal Toxicol 25:531; 2001. 18. Bourland JA, Hayes EF, Kelly RC, Sweeney SA, Hatab MM: Quantitation of cocaine, benzoylecgonine, cocaethylene, methylecgonine, and norcocaine in human hair by positive ion chemical ionization (PICI) gas chromatography-tandem mass spectrometry; J Anal Toxicol 24:489; 2000. 19. Moore C, Guzaldo F, Donahue T: The determination of 11nor-delta-9-tetrahydrocannabinol-9-carboxylic acid (THCCOOH) in hair using negative ion gas chromatographymass spectrometry and high-volume injection; J Anal Toxicol 25:555; 2001. 20. Baptista MJ, Monsanto PV, Marques EGP, Bermejo A, Avila S, Castanheira AM, Margalho C, Barroso M, Vieira DN: Hair analysis for delta-9-THC, delta-9-THC-COOH, CBN and CBD, by GC/MS-EI comparison with GC/MSNCI for Delta-9-THC-COOH; Forensic Sci Int 128:66; 2002. 21. Jurado C, Gimenez MP, Menendez M, Repetto M: Simultaneous quantitation of opiates, cocaine and cannabinoids in hair; Forensic Sci Int 70:165; 1995. 22. Toseland PA: Determination of amphetamine as its Nacetyl derivative by gas-liquid chromatography; Clin Chem Acta 25:75; 1969. 23. Hornbeck CL, Czarny RJ: Quantitation of methamphetamine and amphetamine in urine by capillary GC/MS Part. I. Advantages of trichloroacetyl derivatization; J Anal Toxicol 13:144; 1989. 24. Elian AA: Detection of low levels of flunitrazepam and its metabolites in blood and bloodstains; Forensic Sci Int 101:107; 1999. 25. Hornbeck CL, Carrig JE, Czarny RJ: Detection of a GC/ MS artifact peak as methamphetamine; J Anal Toxicol 17:257; 1993. 26. Reagent insert; Pierce Biotechnology Inc: Rockford, IL; 2003. 27. Gilbert RB, Peng PI, Wong D: A labetalol metabolite with analytical characteristics resembling amphetamines; J Anal Toxicol 19:84; 1995. 28. Gan BK, Baugh D, Liu RH, Walia AS: Simultaneous analysis of amphetamine, methamphetamine, and 3,4-methylenedioxymethamphetamine (MDMA) in urine samples by solidphase extraction, derivatization, and gas chromatography/ mass spectrometry; J Forensic Sci 36:1331; 1991.

29. Cody JT, Schwarzhoff R: Interpretation of methamphetamine and amphetamine enantiomer data; J Anal Toxicol 17:321; 1993. 30. Jones JB, Mell LD: A simple wash procedure for improving chromatography of HFAA derivatized amphetamine extracts for GC/MS analysis; J Anal Toxicol 17:447; 1993. 31. Czarny RJ, Hornbeck CL: Quantitation of methamphetamine and amphetamine in urine by GC/MS Part. II. Derivatization with 4-carbethoxyhexafluorobutyl chloride; J Anal Toxicol 13:257; 1989. 32. Ropero-Miller JD, Lambing MK, Winecker RE: Simultaneous quantitation of opioids in blood by GC-EIMS analysis following deproteination, detautomerization of keto analytes, solid-phase extraction, and trimethylsilyl derivatization; J Anal Toxicol 26:524; 2002. 33. Wang WL, Darwin WD, Cone EJ: Simultaneous assay of cocaine, heroin and metabolites in hair, plasma, saliva and urine by gas chromatography-mass spectrometry; J Chromatogr B Biomed Appl 660:279; 1994. 34. Chen BH, Taylor EH, Pappas AA: Comparison of derivatives for determination of codeine and morphine by gas chromatography/mass spectrometry; J Anal Toxicol 14:12; 1990. 35. Broussard LA, Presley LC, Pittman T, Clouette R, Wimbish GH: Simultaneous identification and quantitation of codeine, morphine, hydrocodone, and hydromorphone in urine as trimethylsilyl and oxime derivatives by gas chromatography-mass spectrometry; Clin Chem 43:1029; 1997. 36. Cremese M, Wu AHB, Cassella G, O’Connor E, Rymut K, Hill DW: Improved GC/MS analysis of opiates with use of oxime-TMS derivatives; J Forensic Sci 43:1220; 1998. 37. Nowatzke W, Zeng J, Sauders A, Bohrer A, Koenig J, Turk J: Distincttttttion among eight opiate drugs in urine by gas chromatography-mass spectrometry; J Pharm Biomed Anal 20:829; 1999. 38. Chen BG, Chang CD, Wang CT, Chang WT, Wang SM, Liu RH: A novel approach to evaluate the extent of crosscontribution to the intensity of ions designating the analyte and the internal standard in quantitative GC-MS analysis; J Am Soc Mass Spectrom 19:598; 2008. 39. Jones J, Tomlinson K, Moore C: The simultaneous determination of codeine, morphine, hydrocodone, hydromorphone, 6-acetylmorphine, and oxycodone in hair and oral fluid; J Anal Toxicol 26:171; 2002. 40. Meatherall R: GC-MS confirmation of codeine, morphine, 6-acetylmorphine, hydrocodone, hydromorphone, oxycodone, and oxymorphone in blood; J Anal Toxicol 29:301; 2005. 41. Fenton J, Mummert J, Childers M: Hydromorphone and hydrocodone interference in GC/MS assays for morphine and codeine; J Anal Toxicol 18:159; 1994. 42. Meatherall R: GC-MS confirmation of codeine, morphine, 6-acetylmorphine, hydrocodone, hydromorphone, oxycodone, and oxymorphone in urine; J Anal Toxicol 23:177; 1999.

Chapter 2 — Chemical Derivatization and Mass Spectrometric Data Collection © 2010 by Taylor and Francis Group, LLC

30

43. Smith ML, Hughes RO, Levine B, Dickerson S, Darwin WD, Cone EJ: Forensic drug testing for opiates. VI. Urine testing for hydromorphone, hydrocodone, oxymorphone, and oxucodone with commercial opiate immunoassays and gas chromatography-mass spectrometry; J Anal Toxicol 19:18; 1995. 44. Broussard LA, Presley LC, Tanous M, Queen C: Improved gas chromatography-mass spectrometry method for simultaneous identification and quantitation of opiates in urine as propionyl and oxime derivatives; Clin Chem 47:127; 2001. 45. Melgar R, Kelly RC: A novel GC/MS derivatization method for amphetamines; J Anal Toxicol 17:399; 1993. 46. Yoo YC, Chung HS, Kim IS, Jin WT, Kim MK: Determination of nalbuphine in drug abusers’ urine; J Anal Toxicol 19:120; 1995. 47. Bioaeronautical Sciences Research Laboratory: Laboratory Operation Manual; U.S. FAA Civil Aerospace Medical Institute: Oklahoma City, OK; 2004.

48. Valentine JL, Middleton R: GC-MS identification of sympathomimetic amine drugs in urine: rapid methodology applicable for emergency clinical toxicology; J Anal Toxicol 24:211; 2000. 49. Low IA, Liu RH, Barker SA, Fish F, Settine RL, Piotrowski EG, Damert WC, Liu JY: Selected ion monitoring mass spectrometry: parameters affecting quantitative determination; Biomed Mass Spectrom 12:633; 1985. 50. Willard HH, Merritt LL, Dean JA, Settle FA: Instrumental Methods of Analysis, 7th ed; Wadsworth Publishing: Belmont, CA; p. 32; 1988. 51. Krull I, Swartz M: Quantitation in method validation. LC•GC 16:1984; 1998. 52. Duncan MW, Gale PJ, Yergey AL: The Principles of Quantitative Mass Spectrometry; Rockpool Productions: Denver, CO; p. 97; 2006.


31

PART TWO MASS SPECTRA OF COMMONLY ABUSED DRUGS AND THEIR ISOTOPICALLY LABELED ANALOGS IN VARIOUS DERIVATIZATION FORMS

Figure I — Stimulants


33

Appendix One Mass Spectra of Commonly Abused Drugs and Their Isotopically Labeled Analogs in Various Derivatization Forms Table of Contents for Appendix One Figure I. Mass spectra of commonly abused drugs and their isotopically labeled analogs in various derivatization forms — Stimulants ......................................................................................................................................................................................

35

Figure II. Mass spectra of commonly abused drugs and their isotopically labeled analogs in various derivatization forms — Opioids .......................................................................................................................................................................................... 129 Figure III. Mass spectra of commonly abused drugs and their isotopically labeled analogs in various derivatization forms — Hallucinogens ................................................................................................................................................................................ 217 Figure IV. Mass spectra of commonly abused drugs and their isotopically labeled analogs in various derivatization forms — Depressants/Hypnotics .................................................................................................................................................................. 251 Figure V. Mass spectra of commonly abused drugs and their isotopically labeled analogs in various derivatization forms — Antianxiety Agents ........................................................................................................................................................................ 273 Figure VI. Mass spectra of commonly abused drugs and their isotopically labeled analogs in various derivatization forms — Antidepresants ............................................................................................................................................................................... 327 Figure VII. Mass spectra of commonly abused drugs and their isotopically labeled analogs in various derivatization forms — Others ............................................................................................................................................................................................ 349



35

Summary of Drugs, Isotopic Analogs, and Chemical Derivatization Groups Included in Figure I (Stimulants) Compound

Isotopic analog

Chemical derivatization group (no. of spectra)

Figure #

Amphetamine

d5, d5 (ring), d6, d8, d10, d11

None, Acetyl, TCA, TFA, PFP, HFB, 4-CB, PFB, propylformyl, l-TPC, d-TPC, l-MTPA, d-MTPA, TMS, t-BDMS, TFA/t-BDMS, PFP/t-BDMS, HFB/t-BDMS (126)

I-1

Methamphetamine

d5, d8, d9, d11, d14

None, acetyl, TCA, TFA, PFP, HFB, 4-CB, PFB, propylformyl, l-TPC, d-TPC, l-MTPA, d-MTPA, TMS, t-BDMS (90)

I-2

Ephedrine

d3

None, acetyl, TCA, [TFA]2, [PFP]2, [HFB]2, 4-CB, PFB, propylformyl, d-TPC, d-MTPA, [TMS]2 (24)

I-3

Phenylpropanolamine

d3

None, acetyl, TCA, [TFA]2, [PFP]2, [HFB]2, 4-CB, PFB, l-TPC, d-TPC, l-MTPA, d-MTPA, [TMS]2, t-BDMS, [t-BDMS]2, TFA/[t-BDMS]2, PFP/[t-BDMS]2, HFB/[t-BDMS]2 (36)

I-4

None, acetyl, TCA, TFA, PFP, HFB, 4-CB, PFB, propylformyl, l-TPC, d-TPC, l-MTPA, d-MTPA, TMS, TFA/t-BDMS, PFP/t-BDMS, HFB/t-BDMS (34)

I-5

MDA

d5

MDMA

d5

None, acetyl, TCA, TFA, PFP, HFB, 4-CB, PFB, propylformyl, l-TPC, d-TPC, l-MTPA, d-MTPA, TMS (28)

I-6

MDEA

d5, d6


I-7

MBDB

d5


I-8

Selegiline

d8

None (2)

I-9

N-Desmethylselegiline d11

None, acetyl, TCA, TFA, PFP, HFB, 4-CB, TMS (16)

I-10

Fenfluramine

d10

None, acetyl, TCA, TFA, PFP, HFB, 4-CB (14)

I-11

Norcocaine

d4

None, TFA, PFP, HFB, TMS (10)

I-12

Cocaine

d3

None (2)

I-13

Cocaethylene

d3, d8

None (3)

I-14

Ecgonine methyl ester

d3

None, TFA, PFP, HFB, TMS, t-BDMS (12)

I-15

Benzoylecgonine

d3, d8

Methyl, ethyl, propyl, butyl, PFPoxy, HFPoxy, TMS, t-BDMS (24)

I-16

Ecgonine

d3

[TMS]2, [t-BDMS]2, HFPoxy/TFA, PFPoxy/PFP, HFPoxy/HFB (10)

I-17

Anhydroecgonine methyl ester

d3

None (2)

I-18

Caffeine

13C

None (2)

I-19

Methylphenidate

d3

None, TFA, PFP, HFB, 4-CB, TMS (12)

I-20

Ritalinic acid

d5

4-CB, [TMS]2, t-BDMS (6)

I-21

3

Total no. of mass spectra: 523



37

Appendix One — Figure I Mass Spectra of Commonly Abused Drugs and Their Isotopically Labeled Analogs in Various Derivatization Forms — Stimulants Figure I-1. Mass spectra of amphetamine and its deuterated analogs (amphetamine-d5, -d5 (ring), -d6, -d8, -d10, -d11): (A) underivatized; (B) acetyl-derivatized; (C) TCA-derivatized; (D) TFA-derivatized; (E) PFP-derivatized; (F) HFB-derivatized; (G) 4-CB-derivatized; (H) PFB-derivatized; (I) propylformyl-derivatized; (J,K) l-TPC-derivatized; (L,M) l-MTPAderivatized; (N)TMS-derivatized; (O) t-BDMS-derivatized; (P) TFA/t-BDMS-derivatized; (Q) PFP/t-BDMS-derivatized; (R) HFB/t-BDMS-derivatized ........................................................................................................................................................ 39 Figure I-2. Mass spectra of methamphetamine and its deuterated analogs (methamphetamine-d5, -d8, -d9, -d11, -d14): (A) underivatized; (B) acetyl-derivatized; (C) TCA-derivatized; (D) TFA-derivatized; (E) PFP-derivatized; (F) HFB-derivatized; (G) 4-CB-derivatized; (H) PFB-derivatized; (I) propylformyl-derivatized; (J,K) l-TPC-derivatized; (L,M) l-MTPAderivatized; (N) TMS-derivatized; (O) t-BDMS-derivatized ......................................................................................................... 57 Figure I-3. Mass spectra of ephedrine and its deuterated analogs (ephedrine-d3): (A) underivatized; (B) acetyl-derivatized; (C) TCA-derivatized; (D) [TFA]2-derivatized; (E) [PFP]2-derivatized; (F) [HFB]2-derivatized; (G) 4-CB-derivatized; (H) PFB-derivatized; (I) propylformyl-derivatized; (J) d-TPC-derivatized; (K) d-MTPA-derivatized; (L) [TMS]2-derivatized ............... 72 Figure I-4. Mass spectra of phenylpropanolamine and its deuterated analogs (phenylpropanolamine-d3): (A) underivatized; (B) acetyl-derivatized; (C) TCA-derivatized; (D) [TFA]2-derivatized; (E) [PFP]2-dervatized; (F) [HFB]2-derivatized; (G) 4-CB-derivatized; (H) PFB-derivatized; (I,J) l-TPC-derivatized; (K,L) l-MTPA-derivatized; (M) [TMS]2-derivatized; (N) t-BDMS-derivatized; (O) [t-BDMS]2-derivatized; (P) TFA/[t-BDMS]2-derivatized; (Q) PFP/[t-BDMS]2-derivatized; (R) HFB/[t-BDMS]2-derivatized ........................................................................................................................................................... 76 Figure I-5. Mass spectra of MDA and its deuterated analogs (MDA-d5): (A) underivatized; (B) acetyl-derivatized; (C) TCA-derivatized; (D) TFA-derivatized; (E) PFP-derivatized; (F) HFB-derivatized; (G) 4-CB-derivatized; (H) PFBderivatized; (I) propylformyl-derivatized; (J,K) l-TPC-derivatized; (L,M) l-MTPA-derivatized; (N) TMS-derivatized; (O) TFA/t-BDMS-derivatized; (P) PFP/t-BDMS-derivatized; (Q) HFB/t-BDMS-derivatized ........................................................... 82 Figure I-6. Mass spectra of MDMA and its deuterated analogs (MDMA-d5): (A) underivatized; (B) acetyl-derivatized; (C) TCA-derivatized; (D) TFA-derivatized; (E) PFP-derivatized; (F) HFB-derivatized; (G) 4-CB-derivatized; (H) PFBderivatized; (I) propylformyl-derivatized; (J,K) l-TPC-derivatized; (L,M) l-MTPA-derivatized; (N) TMS-derivatized ........... 88 Figure I-7. Mass spectra of MDEA and its deuterated analogs (MDEA-d5, -d6): (A) underivatized; (B) acetyl-derivatized; (C) TCA-derivatized; (D) TFA-derivatized; (E) PFP-derivatized; (F) HFB-derivatized; (G) 4-CB-derivatized; (H) PFBderivatized; (I) propylformyl-derivatized; (J,K) l-TPC-derivatized; (L,M) l-MTPA-derivatized; (N) TMS-derivatized ............ 93 Figure I-8. Mass spectra of MBDB and its deuterated analogs (MBDB-d5): (A) underivatized; (B) acetyl-derivatized; (C) TCA-derivatized; (D) TFA-derivatized; (E) PFP-derivatized; (F) HFB-derivatized; (G) 4-CB-derivatized; (H) PFBderivatized; (I) propylformyl-derivatized; (J,K) l-TPC-derivatized; (L,M) l-MTPA-derivatized; (N) TMS-derivatized .......... 100 Figure I-9. Mass spectra of selegiline and its deuterated analogs (selegiline-d8) ....................................................................... 105 Figure I-10. Mass spectra of N-desmethylselegiline and its deuterated analogs (N-desmethylselegiline-d11): (A) underivatized; (B) acetyl-derivatized; (C) TCA-derivatized; (D) TFA-derivatized; (E) PFP-derivatized; (F) HFB-derivatized; (G) 4-CBderivatized; (H) TMS-derivatized ................................................................................................................................................. 106 Figure I-11. Mass spectra of fenfluramine and its deuterated analogs (fenfluramine-d10): (A) underivatized; (B) acetylderivatized; (C) TCA-derivatized; (D) TFA-derivatized; (E) PFP-derivatized; (F) HFB-derivatized; (G) 4-CB-derivatized ............ 109 Figure I-12. Mass spectra of norcocaine and its deuterated analogs (norcocaine-d3): (A) underivatized; (B) TFA-derivatized; (C) PFP-derivatized; (D) HFB-derivatized; (E) TMS-derivatized ..................................................................................... 112 Figure I-13. Mass spectra of cocaine and its deuterated analogs (cocaine-d3) ........................................................................... 114 Figure I-14. Mass spectra of cocaethylene and its deuterated analogs (cocaethylene-d3, -d8) ................................................... 115 Figure I-15. Mass spectra of ecgonine methyl ester and its deuterated analogs (ecgonine methyl ester-d3): (A) underivatized; (B) TFA-derivatized; (C) PFP-derivatized; (D) HFB-derivatized; (E) TMS-derivatized; (F) t-BDMS derivatized .................. 116 Figure I-16. Mass spectra of benzoylecgonine and its deuterated analogs (benzoylecgonine-d3, -d8): (A) methyl-derivatized; (B) ethyl-derivatized; (C) propyl-derivatized; (D) butyl-derivatized; (E) PFPoxy-derivatized; (F) HFBoxy-derivatized; (G) TMS-derivatized; (H) t-BDMS-derivatized .................................................................................................................................... 118 Figure I-17. Mass spectra of ecgonine and its deuterated analogs (ecgonine-d3): (A) [TMS]2-derivatized; (B) [t-BDMS]2derivatized; (C) HFPoxy/TFA-derivatized; (D) PFPoxy/PFP-derivatized; (E) HFPoxy/HFB-derivatized ................................ 122 Figure I-18. Mass spectra of anhydroecgonine methyl ester and its deuterated analogs (anhydroecgonine methyl ester-d3) ............ 124



38

Figure I-19. Mass spectra of caffeine and its deuterated analogs (caffeine-13C3) ...................................................................... 125 Figure I-20. Mass spectra of methylphenidate and its deuterated analogs (methylphenidate-d3): (A) underivatized; (B) TFA-derivatized; (C) PFP-derivatized; (D) HFB-derivatized; (E) 4-CB-derivatized; (F) TMS-derivatized ............................. 126 Figure I-21. Mass spectra of ritalinic acid and its deuterated analogs (ritalinic acid-d5): (A) 4-CB-derivatized; (B) [TMS]2derivatized; (C) t-BDMS-derivatized ........................................................................................................................................... 128

Appendix One — Mass Spectra


39

Figure I-1. Mass spectra of amphetamine (AM) and its deuterated analogs (AM-d5 [ring], -d5 [side chain], -d6, -d8, -d10, -d11): (A) underivatized; (B) acetyl-derivatized; (C) TCA-derivatized; (D) TFA-derivatized; (E) PFP-derivatized; (F) HFB-derivatized; (G) 4-CB-derivatized; (H) PFB-derivatized; (I) propylformylderivatized; (J,K) l-TPC-derivatized; (L,M) l-MTPA-derivatized; (N) TMS-derivatized; (O) t-BDMSderivatized; (P) TFA/t-BDMS-derivatized; (Q) PFP/t-BDMS-derivatized; (R) HFB/t-BDMS-derivatized. Relative Int. (%)

100

44.1

Amphetamine

I-1-A-i

C9H13N MW: 135.21

NH2 CH 2 –CH–CH 3

50 92.1

120.1

0 40 Relative Int. (%)

100

90 44.0

140 Amphetamine-d5

I-1-A-ii D

D

50 D

96.0

NH2 CH 2 –CH–CH 3

C9H8D5N MW: 140.24

D D

125.1


100

90 48.1

140 Amphetamine-d5

I-1-A-iii

C9H8D5N MW: 140.24

H

NH2 CD–CD–CD 3

50 92.0

122.1


100

90 48.1

140 Amphetamine-d6

I-1-A-iv

NH2 CD 2 –CD–CD 3

C9H7D6N MW: 141.24

50 93.0

123.1


100

90 47.1

140

I-1-A-v

Amphetamine-d8 D

D

NH2 CH 2 –CH–CD 3

C9H5D8N MW: 143.25

50 D

D D

96.1

125.1


100

90 48.1

140 Amphetamine-d10

I-1-A-vi D D

H

NH2 CD–CD–CD 3

50 D

97.1

D

D

127.1

0 40 100 Relative Int. (%)

C9H3D10N MW: 145.27

90 48.1

140

I-1-A-vii D

50

D

98.1

D

NH2 CD 2 –CD–CD 3

Amphetamine-d11 C9H2D11N MW: 146.27

D D

128.1

0 40

90

140 m/z



40

Figure I-1. (Continued) Relative Int. (%)

100

44.1

Amphetamine, acetyl derivative

I-1-B-i 86.1

NHCOCH3

118.1

50

C11H15NO MW: 177.24

CH 2 –CH–CH 3

91.1


100

90 44.1

140

190

I-1-B-ii

Amphetamine-d5, acetyl derivative 86.1 D

123.1

50

NHCOCH3

D

CH 2 –CH–CH 3

C11H10D5NO MW: 182.27

96.1 D

D D

0 Relative Int. (%)

100

40 48.1

I-1-B-iii

90

140

190 Amphetamine-d5, acetyl derivative

90.1

H

50

NHCOCH3

CD–CD–CD 3

122.1

C11H10D5NO MW: 182.27

92.1


100

90 48.1

140

190

I-1-B-iv

Amphetamine-d6, acetyl derivative 90.1

H

123.1

50

NHCOCH3

CD 2 –CD–CD 3

C11H9D6NO MW: 183.28

93.1


100

90 47.1

140

190

I-1-B-v


50

D

126.1 96.1

D

NHCOCH3

D

CH 2 –CH–CD 3

C11H7D8NO MW: 185.29

D D

0 Relative Int. (%)

100

40

90 48.1

140

190

I-1-B-vi


D

50

D

97.1

H

NHCOCH3

CD–CD–CD 3

C11H5D10NO MW: 187.30

127.1 D

D

D


100

90 48.1

140

190

I-1-B-vii


50

D

128.1

98.1 70.1

D

D

NHCOCH3 CD 2 –CD–CD 3

C11H4D11NO MW: 188.31

D D

0 40

90

140 m/z Appendix One — Mass Spectra


190

41


100

I-1-C-i

118.1

Amphetamine, trichloroacetyl derivative

91.1

188.0

NHCOCCl3

50

CH 2 –CH–CH 3

C11H12Cl3NO MW: 280.58


100

100

150

200

250

123.0

I-1-C-ii

188.0

96.0

D

50

D

300

Amphetamine-d5, trichloroacetyl derivative NHCOCCl 3

D

C11H7D5Cl3NO MW: 285.61

CH 2 –CH–CH 3 D D

0 50

100

150

Relative Int. (%)

100

200

250

192.0

I-1-C-iii

123.1

H

92.1

50

300

Amphetamine-d5, trichloroacetyl derivative NHCOCCl3

CD–CD–CD 3

C11H7D5Cl3NO MW: 285.61


100

100

150

200

250

123.1

I-1-C-iv

Amphetamine-d6, trichloroacetyl derivative

192.0

93.1

300

NHCOCCl3 CD 2 –CD–CD 3

50

C11H6D6Cl3NO MW: 286.61

0 50

100

Relative Int. (%)

100

150

200

126.2

I-1-C-v

300


191.0

50

250

D

CH 2 –CH–CD 3

96.1 D

NHCOCCl3

D

C11H4D8Cl3NO MW: 288.63

D D


100

100

I-1-C-vi

150

200

250

192.0

128.1 97.1

D D

50

D

D

H

300

Amphetamine-d10, trichloroacetyl derivative NHCOCCl 3

CD–CD–CD 3

C11H2D10Cl3NO MW: 290.64

D

0 50

100

Relative Int. (%)

100

I-1-C-vii

150

200

250

128.2

300


98.1

192.0 D

50

D

D

NHCOCCl3 CD 2 –CD–CD 3

C11HD11Cl3NO MW: 291.64

D D

0 50

100

150

200 m/z



250

300

42


100

I-1-D-i

140.1

118.1

Amphetamine, trifluoroacetyl derivative NHCOCF3

91.1

50

CH 2 –CH–CH 3

C11H12F3NO MW: 231.21


100

100

I-1-D-ii

50

150 123.1

200

140.0

Amphetamine-d5, trifluoroacetyl derivative D

96.1

250

D

NHCOCF3

D

CH 2 –CH–CH 3

C11H7D5F3NO MW: 236.24

D D


100

100

150

200

144.1

I-1-D-iii

H

50

92.1

Amphetamine-d5, trifluoroacetyl derivative NHCOCF3

CD–CD–CD 3

123.1

250

C11H7D5F3NO MW: 236.24


100

100

I-1-D-iv

150

200

144.1

Amphetamine-d6, trifluoroacetyl derivative

123.1

50

NHCOCF3

CD 2 –CD–CD 3

93.1

250

C11H6D6F3NO MW: 237.25


100

100 126.1

I-1-D-v

50

150

200

143.1


D

96.1

250

D

NHCOCF3

D

CH 2 –CH–CD 3

C11H4D8F3NO MW: 239.26

D D


100

100

I-1-D-vi

150

200

144.1


D

50

97.1

D

128.1 D

D

H

NHCOCF3

CD–CD–CD 3

250

C11H2D10F3NO MW: 241.27

D


100

100

150

I-1-D-vii

200

144.1


128.2 D

98.1

50

250

D

D

NHCOCF3 CD 2 –CD–CD 3

C11HD11F3NO MW: 242.28

D D

0 50

100

150 m/z



200

250

43


100

190.1

I-1-E-i

50

Amphetamine, pentafluoropropionyl derivative

118.1

NHCOC 2F5 CH 2 –CH–CH 3

91.1

C12H12F5NO MW: 281.22

0 50 Relative Int.(%)

100

100

150

200

250

190.0

I-1-E-ii

300

Amphetamine-d5, pentafluoropropionyl derivative

123.1 D

50 96.1 119.0

D

NHCOC 2F5

D

CH 2 –CH–CH 3

C12H7D5F5NO MW: 286.25

D D


100

100

150

200

250

194.1

I-1-E-iii

Amphetamine-d5, pentafluoropropionyl derivative H NHCOC 2F5 CD–CD–CD 3

123.2

50 92.1

300

C12H7D5F5NO MW: 286.25

119.0


100

100

150

250

194.1

I-1-E-iv

50

200

300


123.1

NHCOC 2F5 CD 2 –CD–CD 3

93.1

C12H6D6F5NO MW: 287.26

119.0


100

100

150

I-1-E-v

200

250

193.1

126.2

300


D

50 96.1 119.0

D

NHCOC 2F5

D

C12H4D8F5NO MW: 289.27

CH 2 –CH–CD 3

D D


100

100

150

200

250

194.1

I-1-E-vi

Amphetamine-d10, pentafluoropropionyl derivative D

127.2

50

300

D

97.1 119.1

D

D

H

NHCOC 2F5

CD–CD–CD 3

C12H2D10F5NO MW: 291.28

D


100

100

150

200

250

194.1

I-1-E-vii


128.1 D

50

300

D

98.1 D

119.1


C12HD11F5NO MW: 292.29

D D

0 50

100

150

200 m/z



250

300

44


100

Amphetamine, heptafluorobutyryl derivative

240.1

I-1-F-i 118.1


50 91.1

C13H12F7NO MW: 331.23

169.0


100

100

150

200

250

300

Amphetamine-d5, heptafluorobutyryl derivative

240.0

I-1-F-ii 123.1

D

50 96.1

D

169.0

350


D

C13H7D5F7NO MW: 336.26

D D

0 50

100

150

200

Relative Int. (%)

100

I-1-F-iii 50

250

300

H NHCOC 3F7 CD–CD–CD 3

123.1 92.1

350


244.1

C13H7D5F7NO MW: 336.26

169.0


100

100

I-1-F-iv

50

150

200

250

300

244.1

123.1

350

Amphetamine-d6, heptafluorobutyryl derivative NHCOC 3F7 CD 2 –CD–CD 3

93.1

C13H6D6F7NO MW: 337.27

169.0

0 50

100

150

200

Relative Int. (%)

100

250

300


243.1

I-1-F-v

126.2 D

50 96.1

D

169.0

350

NHCOC 3F7 CH 2 –CH–CD 3

D

C13H4D8F7NO MW: 339.28

D D

0 50

100

150

200

Relative Int. (%)

100

250

I-1-F-vi

350

Amphetamine-d10, heptafluorobutyryl derivative H

NHCOC 3F7 CD–CD–CD 3

D

128.2

50

300

244.1

D

C13H2D10F7NO MW: 341.29

97.1 D

169.0

D

D

0 50

100

150

200

Relative Int. (%)

100

I-1-F-vii

250

300

128.2 D

50

350


244.1

D

98.1 D

169.0


C13HD11F7NO MW: 342.30

D D

0 50

100

150

200 m/z



250

300

350

45


100

118.1

I-1-G-i

Amphetamine, 4-carboethoxyhexafluorobutyryl derivative

NHCO(CF2)3COOC2H5

50

CH 2 –CH–CH 3

91.1

266.1

248.0

294.1

C16H17F6NO3 MW: 385.30

220.0

195.0


100

100

150

200

I-1-G-ii

D

50

96.1

D

D D

Relative Int. (%)

100

150

250

294.0

300

123.1

I-1-G-iii

H

NHCO(CF2)3COOC2H5

270.1

298.1

CD–CD–CD 3

92.1

50

266.0

248.0 220.0

200

350

400

Amphetamine-d5, 4-carboethoxyhexafluorobutyryl derivative

CH 2 –CH–CH 3

195.0

50

300

NHCO(CF2)3COOC2H5

D

0

100

250

123.1

251.1

C16H12D5F6NO3 MW: 390.33

350

400

Amphetamine-d5, 4-carboethoxyhexafluorobutyryl derivative C16H12D5F6NO3 MW: 390.33

223.0

195.0


100

100

I-1-G-iv

150

200

250

NHCO(CF2)3COOC2H5 CD 2 –CD–CD 3

50

300

123.1 270.1

298.1

350

400


93.1 251.1 223.0

195.0


100

100

150

200

250

300

126.1

I-1-G-v

D

CH 2 –CH–CD 3

50

269.1 96.1

D

D

297.1

C16H9D8F6NO3 MW: 393.35

250.1

D

400


NHCO(CF2)3COOC2H5

D

350

223.1

195.0

0 Relative Int. (%)

100

50

100

I-1-G-vi 97.1

50

150

200

250

300

350

400

128.2 D D

D

H

NHCO(CF2)3COOC2H5

270.1

298.1

CD–CD–CD 3

251.1

D D

C16H7D10F6NO3 MW: 395.36

223.0

195.0



100

100

150

200

I-1-G-vii

300

D D

NHCO(CF2)3COOC2H5

D

CD 2 –CD–CD 3

98.1

50

250

128.2 298.1 270.1

D

400


251.1

D

350

223.0

195.0

0 50

100

150

200

250 m/z



300

350

400

46

Figure I-1. (Continued) Relative Int.(%)

100

Amphetamine, 2,3,4,5,6pentafluorobenzoyl derivative

195.0

I-1-H-i

238.0

50

NHCOC 6F5

C16H12F5NO MW: 329.26

CH 2 –CH–CH 3

118.1 167.0

91.1

0 50

100

150

200

Relative Int. (%)

100

250

300

195.0

I-1-H-ii

Amphetamine-d5, 2,3,4,5,6pentafluorobenzoyl derivative 238.0

50

D

D

123.1 167.0

96.1

350

D


C16H7D5F5NO MW: 334.29

D D


100

100

150

200

250

300

I-1-H-iii

50

350

Amphetamine-d5, 2,3,4,5,6pentafluorobenzoyl derivative

195.0

H

242.0

NHCOC 6F5

C16H7D5F5NO MW: 334.29

CD–CD–CD 3

92.1

167.0

123.1

0 50

100

150

200

Relative Int. (%)

100

250

300

195.0

I-1-H-iv

NHCOC 6F5

242.0

50

350

Amphetamine-d6, 2,3,4,5,6pentafluorobenzoyl derivative C16H6D6F5NO MW: 335.30

CD 2 –CD–CD 3

123.1

167.0

93.1


100

100

150

200

250

300

195.0

I-1-H-v


241.0

50

D

D

126.1 167.0

96.1

350

D

NHCOC 6F5 CH 2 –CH–CD 3

C16H4D8F5NO MW: 337.31

D D


100

100

150

200

250

300

195.0

I-1-H-vi

Amphetamine-d10, 2,3,4,5,6pentafluorobenzoyl derivative 242.0

50 97.1

128.2

350

167.0

D D D

D

H

NHCOC 6F5 CD–CD–CD 3

C16H2D10F5NO MW: 339.33

D


100

100

150

200

250

300

I-1-H-vii

242.0

50 128.2

167.0

98.1

350


195.0

D D

D


C16HD11F5NO MW: 340.33

D D

0 50

100

150

200 m/z



250

300

350

47


100

I-1-I-i

Amphetamine, propylformyl derivative

130.1 NHCOOC3H7

50

C13H19NO2 MW: 221.30

CH 2 –CH–CH 3

91.0

0

Relative Int. (%)

50 100

100

I-1-I-ii

150

200

130.1 96.1

D

C13H14D5NO2 MW: 226.33

CH 2 –CH–CH 3

50 D

NHCOOC3H7

D

250

Amphetamine-d5, propylformyl derivative

D D


100

100

I-1-I-iii

150

200

134.1 H

NHCOOC3H7

Amphetamine-d5, propylformyl derivative C13H14D5NO2 MW: 226.33

CD–CD–CD 3

50

250

92.0


100

100

150

200

134.1

I-1-I-iv

NHCOOC3H7

C13H13D6NO2 MW: 227.33

CD 2 –CD–CD 3

50

250


93.0

0 50 Reative Int. (%)

100

100

150 133.1

I-1-I-v

D

50

200

96.1

NHCOOC3H7

D

CH 2 –CH–CD 3

C13H11D8NO2 MW: 229.34

D

D

250


D


100

100

150 134.1

I-1-I-vi

D D

50

200

97.1

D

D

H

NHCOOC3H7

250


CD–CD–CD 3

C13H9D10NO2 MW: 231.36

D


100

100

150

200

134.1

I-1-I-vii

D

D

98.1

50

D

NHCOOC3H7

250


CD 2 –CD–CD 3

C13H8D11NO2 MW: 232.36

D D

0 50


100

150 m/z Figure I — Stimulants

200

250

48


100 CH 2 CH

50

l-Amphetamine, (S)-(–)-N(trifluoroacetyl)-prolyl derivative

166.0

O NH C

I-1-J-i

N O CCF 3

C16H19F3N2O2 MW: 328.33

237.1

CH 3

194.0

91.0

118.0

0 50

100

Relative Int. (%)

100

150

O D

CH 2 CH

50 D

D

250

I-1-J-ii

N

300

350

l-Amphetamine-d5, (S)-(–)-N(trifluoroacetyl)-prolyl derivative C16H14D5F3N2O2 MW: 333.36

O CCF 3

CH 3

D

166.1

C

NH

D

200

96.1

237.1

194.0

123.1

0 50

100

Relative Int. (%)

100

150 166.0

O H NH C CD

50

CD

200

250

N

CD 3

92.0

C16H14D5F3N2O2 MW: 333.36

241.1

194.0

350

l-Amphetamine-d5, (S)-(–)-N(trifluoroacetyl)-prolyl derivative

I-1-J-iii

O CCF 3

300

123.1

0 50

100

Relative Int. (%)

100

150

NH C CD 2 CD

50

200 166.0

O

250

I-1-J-iv

N O CCF 3

CD 3

350

C16H13D6F3N2O2 MW: 334.37

241.1

194.0 93.0

300


123.1

0 50

100

150

Relative Int. (%)

100

166.0

O D

50

D

NH C

D

CH 2 CH D

D

200

250

300


I-1-J-v

N

O CCF 3

CD 3

C16H11D8F3N2O2 MW: 336.38

240.1

194.0

350

126.1

96.0

0 50

100

Relative Int. (%)

100

150

O D

D

CD

50 D

H

D

D

NH C CD

200 166.0

250

N

C16H9D10F3N2O2 MW: 338.39

241.1 194.0

97.1

350


I-1-J-vi

O CCF 3

CD 3

300

128.1

0 50

100

Relative Int. (%)

100

150

O

D

D

CD 2 CD

50 D

NH C

D

D

200

250

166.0

I-1-J-vii

N O CCF 3

CD 3

98.1

300

350

l-Amphetamine-d11, (S)-(–)-N(trifluoroacetyl)-prolyl derivative C16H8D11F3N2O2 MW: 339.40

241.1 194.0 128.1

0 50

100

150

200 m/z



250

300

350

49


100

O

166.0

NH C CH 2 CH

50

I-1-K-i

N

d-Amphetamine, (S)-(–)-N(trifluoroacetyl)-prolyl derivative C16H19F3N2O2 MW: 328.33

O CCF 3

CH 3

194.0

91.0

237.1

118.0

0 50

100

Relative Int. (%)

100

150

O D

CH 2 CH

50 D

D

I-1-K-ii

N

300

350

d-Amphetamine-d5, (S)-(–)-N(trifluoroacetyl)-prolyl derivative C16H14D5F3N2O2 MW: 333.36

O CCF 3

CH 3

D

250

166.1

NH C

D

200

96.1

194.0

123.1

237.1

0 50

100

Relative Int. (%)

100

150

O

166.0

H NH C CD

50

CD

200

250

I-1-K-iii

N O CCF 3

300

C16H14D5F3N2O2 MW: 333.36

241.1

CD 3

350

d-Amphetamine-d5, (S)-(–)-N(trifluoroacetyl)-prolyl derivative

194.0

92.0

123.1

0 50

100

Relative Int. (%)

100

150

O

166.0

NH C CD 2 CD

50

200

250

I-1-K-iv

N

300


O CCF 3

CD 3

350

241.1 194.0

93.0

123.1

0 50

100

Relative Int. (%)

100

150 166.0

O D

CH 2 CH

50 D

NH C

D

D

D

200

250

I-1-K-v

N O CCF 3

300

C16H11D8F3N2O2 MW: 336.38

240.1

CD 3

350

d-Amphetamine-d8, (S)-(–)-N(trifluoroacetyl)-prolyl derivative

194.0 96.0

126.1

0 50

100

Relative Int. (%)

100

150 166.0

O D

D

50 D

D

H

NH

CD

CD

D

C

CD 3

200

250

I-1-K-vi

N O CCF 3

300

350


241.1 194.0

97.1

128.1

0 50

100

Relative Int. (%)

100

150 166.0

O D

CD 2 CD

50 D

NH C

D

D

D

200

I-1-K-vii

N O CCF 3

CD 3

98.1

250

194.0

300

350


241.1

128.1

0 50

100

150

200 m/z



250

300

350

50


100

l-Amphetamine, (–)-α-methoxy-α-trifluoromethylphenylacetyl derivative

189.0

I-1-L-i 91.0

260.0

50

119.0

C19H20F3NO2 MW: 351.36

NHCOC(CF3)(C6H5)OCH3 CH 2 –CH–CH 3

234.0

162.1

351.1


100

100

150

200

I-1-L-ii

250

300

260.0 124.1

D

234.0

167.1

D


100

150

200

CH 2 –CH–CH 3 D

356.2

D

250

300

350

400

l-Amphetamine-d5, (–)-α-methoxy-α-trifluoromethylphenylacetyl derivative

264.1 93.0

C19H15D5F3NO2 MW: 356.39

NHCOC(CF3)(C6H5)OCH3

D

189.0

I-1-L-iii

50

400


96.1

50

100

350

189.0

H

124.1


CD–CD–CD 3

167.1

C19H15D5F3NO2 MW: 356.39

235.0

356.2


100

100

150

200

250

300

189.0

I-1-L-iv 93.0

50

350


264.1


125.1

CD 2 –CD–CD 3

168.1

400

C19H14D6F3NO2 MW: 357.40

236.0

357.2


100

100

150

200

250

300

189.0

I-1-L-v 97.1

127.1

D

170.1

235.0

400


263.1

50

350

D


D

CH 2 –CH–CD 3

C19H12D8F3NO2 MW: 359.41

D

359.2

D

0 Relative Int. (%)

100

50

100

150

200

250

300

189.0

I-1-L-vi 97.1

D

129.1 172.1

D

236.0

400


264.1

50

350

D

H


CD–CD–CD 3

C19H10D10F3NO2 MW: 361.42

D

361.2

D

0 Relative Int. (%)

100

50

100

150

200

250

300

189.0

I-1-L-vii

264.1 D

130.1 173.1

D

236.0

400


98.1

50

350


D

CD 2 –CD–CD 3

C19H9D11F3NO2 MW: 362.43

D D

362.2

0 50

100

150

200

250 m/z



300

350

400

51


100

189.0 91.0

d-Amphetamine, (–)-α-methoxy-α-trifluoromethylphenylacetyl derivative

I-1-M-i 260.0

50

119.0

C19H20F3NO2 MW: 351.36


162.1

CH 2 –CH–CH 3

234.0

351.1

0 50

100

150

Relative Int. (%)

100

200 189.0

250

260.0 124.1

D D

CH 2 –CH–CH 3 D

356.1

D

0 Relative Int. (%)

100

50

100

150

200 189.0

250

300

93.0

I-1-M-iii H

124.1

350

C19H15D5F3NO2 MW: 356.39


CD–CD–CD 3

167.1 235.0

356.1

0 50

100

150

Relative Int. (%)

100

200 189.0

250

300

264.1

50 125.1

350


168.1

CD 2 –CD–CD 3

C19H14D6F3NO2 MW: 357.40

236.0

357.1

0 50

100

150

Relative Int. (%)

100

200 189.0

250

300

I-1-M-v

97.1

127.1

D

170.1 235.0

D

350


D

CH 2 –CH–CD 3

C19H12D8F3NO2 MW: 359.41

D

359.1

D

0 50

100

150

Relative Int. (%)

100

200 189.0

250

300

I-1-M-vi

97.1

129.1

D

D

D

H


CD–CD–CD 3

172.1 235.0

350

C19H10D10F3NO2 MW: 361.42

D

361.1

D

0 50

100

150

Relative Int. (%)

100

200 189.0

50

250

300

264.1 130.1

D

173.1

236.0

D

350


D

CD 2 –CD–CD 3

C19H9D11F3NO2 MW: 362.43

D

362.2

D

0 50


100

150

200


400

d-Amphetamine-d11, (–)-α-methoxy-α-trifluoromethylphenylacetyl derivative

I-1-M-vii

98.1

400


264.1

50

400


263.1

50

400


I-1-M-iv

93.0

400


264.1

50

400

C19H15D5F3NO2 MW: 356.39


D

234.0

167.1

350


I-1-M-ii

96.1

50

300

300

350

400

52


100

Amphetamine, trimethylsilyl derivative

116.2

I-1-N-i

NHSi(CH3)3

73.1

50

C12H21NSi MW: 207.39

CH 2 –CH–CH 3

91.1

192.2

100.1

0 50 Relatine Int. (%)

100

100

150

I-1-N-ii

D

50

200

116.1 CH 2 –CH–CH 3

73.1 D

96.1

NHSi(CH3)3

D

250

Amphetamine-d5, trimethylsilyl derivative C12H16D5NSi MW: 212.42

D D

197.2

100.1


100

100

150

200

120.2

I-1-N-iii

H

50

NHSi(CH3)3

250


CD–CD–CD 3

73.1 92.1

197.2

104.1


100

100

150

I-1-N-iv

200

120.2 NHSi(CH3)3

250


CD 2 –CD–CD 3

50

73.1 93.1

198.2

104.1


100

100

150

I-1-N-v

D

50

200

119.2

D

103.1

C12H13D8NSi MW: 215.44

CH 2 –CH–CD 3

73.1 96.1

NHSi(CH3)3

D

250

Amphetamine-d8, trimethylsilyl derivative

D D

200.2


100

100

150

200

120.2

I-1-N-vi

D

50

D

73.1

D

97.2

104.1

D

H

NHSi(CH3)3

250


CD–CD–CD 3 D

202.2


100

100

150

I-1-N-vii

D

50

200

120.2 D

73.1 D

98.2

104.1

NHSi(CH3)3

250


CD 2 –CD–CD 3 D

D

203.2

0 50


100


200

250

53


100

158.1

I-1-O-i

50

Amphetamine, t-butyldimethylsilyl derivative

NHSi(CH3)2C(CH ) 3 3 CH 2 –CH–CH 3

C15H27NSi MW: 249.47

73.1 100.1

192.1 234.2


100

100

I-1-O-ii

150

200

158.1

Amphetamine-d5, t-butyldimethylsilyl derivative

250

D

C15H22D5NSi MW: 254.50

50 73.1 100.1

D

300 NHSi(CH3)2C(CH ) 3 3

D

CH 2 –CH–CH 3

D D

197.1 239.2


100

100

150 162.1

I-1-O-iii

50

200

250


H

197.2

104.1

239.2


100

100

150 162.2

I-1-O-iv

50

200

250


NHSi(CH3)2C(CH3)3

C15H21D6NSi MW: 255.50

73.1

300

CD 2 –CD–CD 3

198.2

104.1

240.2


NHSi(CH3)2C(CH ) 3 3

CD–CD–CD 3

C15H22D5NSi MW: 254.50

73.1

300

100

150 161.2

I-1-O-v

50

200 Amphetamine-d8, t-butyldimethylsilyl derivative C15H19D8NSi MW: 257.58

73.1 103.1

250

D D

300 NHSi(CH3)2C(CH ) 3 3

D

CH 2 –CH–CD 3

D D

200.2 242.2


100

100

150 162.2

I-1-O-vi

50

200 Amphetamine-d10, t-butyldimethylsilyl derivative C15H17D10NSi MW: 259.53

73.1

250

D

D

D

244.2


NHSi(CH3)2C(CH ) 3 3

CD–CD–CD 3

D

202.2

104.1

H

D

300

100

150 162.2

I-1-O -vii

200

C15H16D11NSi MW: 260.53

50 73.1

250


203.2

104.1

D D

300 NHSi(CH3)2C(CH ) 3 3

D

CD 2 –CD–CD 3 D

D

245.2

0 50

100

150

200 m/z



250

300

54


100

73.0

50

Amphetamine, trifluoroacetyl/ t-butyldimethylsilyl derivative

254.1

I-1-P-i

COCF 3 NSi(CH3)2C(CH3) 3 CH 2 –CH–CH 3

91.0

C17H26F3NOSi MW: 345.48 288.1

119.1

0 50

100

Relative Int. (%)

100

73.0

150

200

I-1-P-ii D

D

124.1 D

300 254.1

COCF 3

96.1

50

250

350

400

Amphetamine-d5, trifluoroacetyl/ t-butyldimethylsilyl derivative

NSi(CH3)2C(CH3) 3 CH 2 –CH–CH 3

C17H21D5F3NOSi MW: 350.51 293.1

D D

0 50

100

150

200

250

Relative Int. (%)

100

I-1-P-iii

73.0

300 258.1

COCF 3 NSi(CH3)2C(CH3) 3 CD–CD–CD 3 H

50

93.1

124.1

350

400

Amphetamine-d5, trifluoroacetyl/ t-butyldimethylsilyl derivative C17H21D5F3NOSi MW: 350.51

293.1

0 50

100

Relative Int. (%)

100

150

200

73.0

300 258.1

I-1-P-iv

50

250

NSi(CH3)2C(CH3)3 CD 2 –CD–CD 3

125.1

400


COCF 3

93.1

350

C17H20D6F3NOSi MW: 351.51

294.1

0 50

100

150

200

Relative Int. (%)

100

I-1-P-v 73.0

D

D

50 97.1

127.1

D

250

COCF 3 NSi(CH3)2C(CH3) 3 CH 2 –CH–CD 3

D

300 257.1

350

400

Amphetamine-d8, trifluoroacetyl/ t-butyldimethylsilyl derivative C17H18D8F3NOSi MW: 353.52

296.1

D

0 50

100

150

200

Relative Int. (%)

100

I-1-P-vi D

73.0

50

D

97.1

129.1

D

D

250

300 258.1

COCF 3 NSi(CH3)2C(CH3) 3 CD–CD–CD 3

350

400


H

C17H16D10F3NOSi MW: 355.54

D

298.1

0 50

100

150

200

250

Relative Int. (%)

100

I-1-P-vii 73.0

50

98.1 D

D

130.1 D

COCF 3 NSi(CH3)2C(CH3) 3 CD 2 –CD–CD 3

300 258.1

350

400

Amphetamine-d11, trifluoroacetyl/ t-butyldimethylsilyl derivative C17H15D11F3NOSi MW: 356.54 299.1

D D

0 50


100

150

200


300

350

400

55


100

304.1

I-1-Q-i

NSi(CH3)2C(CH3) 3 CH 2 –CH–CH 3

73.0 91.1

50

Amphetamine, pentafluoropropionyl/t-butyldimethylsilyl derivative

COC 2 F 5

119.1

C18H26F5NOSi MW: 395.48 338.1

0 50

100

Relative Int. (%)

100

150

200

50

96.1

D

D

343.1

200

250

300

Relative Int. (%)

100

93.1

H NSi(CH3)2C(CH3) 3 CD–CD–CD 3

124.1

400

450

Amphetamine-d5, pentafluoropropionyl/t-butyldimethylsilyl derivative

COC 2 F 5

73.0

50

350 308.1

I-1-Q-iii

450


D

150

400


NSi(CH3)2C(CH3) 3 CH 2 –CH–CH 3 D

D

0 100

350

COC 2 F 5

124.1

50

300 304.1

I-1-Q-ii 73.0

250


343.1

0 50

100

Relative Int. (%)

100

150

200

73.0

300

350

COC 2 F 5 NSi(CH3)2C(CH3)3 CD 2 –CD–CD 3

93.1

400

450


308.1

I-1-Q-iv

50

250


125.1

344.1

0 50

100

Relative Int. (%)

100

150

200

I-1-Q-v 73.0

50

127.1

300

D

400

450


NSi(CH3)2C(CH3) 3 CH 2 –CH–CD 3


D

D

350 307.1

COC 2 F 5

D

97.1

250

346.1

D

0 50

100

Relative Int. (%)

100

150

200

D

COC 2 F 5 NSi(CH3)2C(CH3) 3 CD–CD–CD 3

D

D

73.0

D

98.1

300

350 308.1

I-1-Q-vi

50

250

H

450

C18H16D10F5NOSi MW: 405.54

129.1 D

400


348.1

0 50

100

Relative Int. (%)

100 98.1

150

D

250

300

350 308.1

I-1-Q-vii

73.0

50

200

NSi(CH3)2C(CH3) 3 CD 2 –CD–CD 3

C18H15D11F5NOSi MW: 406.55

130.1 D

450


COC 2 F 5

D

400

D

349.1

D

0 50


100

150

200


300

350

400

450

56


100

I-1-R-i

Amphetamine, heptafluorobutyryl/ t-butyldimethylsilyl derivative

NSi(CH3)2C(CH3)3 CH 2 –CH–CH 3

73.0 91.0

50

354.1

COC 3 F 7

C19H26F7NOSi MW: 445.49

119.1

388.1

0 50

100

150

Relative Int. (%)

100

200

250

I-1-R-ii 73.0

50

D

96.1 124.1

D

300

354.1

COC 3 F 7 D

350

400

450

500

Amphetamine-d5, heptafluorobutyryl/ t-butyldimethylsilyl derivative

NSi(CH3)2C(CH3)3 CH 2 –CH–CH 3


D

393.1

D

0 50

100

150

Relative Int. (%)

100

200

250

350 358.1

I-1-R-iii

50

300

COC 3 F 7

400

93.0

500


H NSi(CH3)2C(CH3)3 CD–CD–CD 3

73.0

450


124.1

393.1

0 50

100

150

Relative Int. (%)

100

200

250

350 358.1

I-1-R-iv

COC 3 F 7

400

450

500



73.0 93.0

50

300


125.1

394.1

0 50

100

150

Relative Int. (%)

100

200

250

I-1-R-v D

73.0

50

97.1

127.1

D

300

357.1

COC 3 F 7 D

350

400

450

500


NSi(CH3)2C(CH3)3 CH 2 –CH–CD 3


D

396.1

D

0 50

100

150

Relative Int. (%)

100

200

250

50

D

98.1

350 358.1

I-1-R-vi 73.0

300

COC 3 F 7 D

400

NSi(CH3)2C(CH3)3 CD–CD–CD 3 H

500

C19H16D10F7NOSi MW: 455.55

129.1 D

450


D

398.1

D

0 50

100

150

200

250

300

Relative Int. (%)

100

I-1-R-vii 98.1 73.0

50

D

130.1

D

350 358.1

COC 3 F 7 D

400

450

500



C19H15D11F7NOSi MW: 456.56

D

399.1

D

0 50

100

150

200

250

300 m/z



350

400

450

500

57

Figure I-2. Mass spectra of methamphetamine (MA) and its deuterated analogs (MA-d5, -d8, -d9, -d11, -d14): (A) underivatized; (B) acetyl-derivatized; (C) TCA-derivatized; (D) TFA-derivatized; (E) PFP-derivatized; (F) HFBderivatized; (G) 4-CB-derivatized; (H) PFB-derivatized; (I) propylformyl-derivatized; (J,K) l-TPC-derivatized; (L,M) l-MTPA-derivatized; (N) TMS-derivatized; (O) t-BDMS-derivatized.

Relative Int. (%)

100

I-2-A-i

58.1

Methamphetamine CH 3 CH 2 –CH–CH 3

50 91.0

134.1

0 50

100 Relative Int. (%)

C10H15N MW: 149.23

NH

100 62.1

150

200 Methamphetamine-d5

I-2-A-ii

CD 3

C10H10D5N MW: 154.26

NH

D

CH–CD–CH 3

50 92.0

139.1


100

100 65.1

150

I-2-A-iii

D

C10H7D8N MW: 157.28

NH

CH–CD–CD 3

50 92.0


CD 3

139.1


100

100 65.1

150


I-2-A-iv

CD 3

C10H6D9N MW: 158.29

NH CD 2 –CD–CD 3

50 93.0

140.1


100

100 64.1

150 CD 3

I-2-A-v D

CH 2 –CH–CD 3

50 D

96.1

D D

142.1


100

100 65.1

C10H4D11N MW: 160.30

NH

D


150 CD 3

I-2-A-vi D

50

D

98.1

D

200 Methamphetamine-d14 C10HD14N MW: 163.32

NH CD 2 –CD–CD 3 D

D

145.1

0 50

100

150 m/z



200

58


100

58.1

I-2-B-i

CH 3

C12H17NO MW: 191.27

NCOCH3

50

CH 2 –CH–CH 3

91.1 134.1

0 50


Methamphetamine, acetyl derivative

100.1

100 62.1

I-2-B-ii

150

200

Methamphetamine-d5, acetyl derivative

CD 3

104.1

C12H12D5NO MW: 196.30

D

NCOCH3 CH–CD–CH 3

50 92.1

250

139.1


100

100 65.2

150

I-2-B-iii

NCOCH3 D CH–CD–CD 3

50 92.1


100

I-2-B-iv

150

200

NCOCH3 CD 2 –CD–CD 3

50 93.1

50 100

I-2-B-v

150

50

D

97.1

100 65.1

D

250 Methamphetamine-d11, acetyl derivative

NCOCH3 CH 2 –CH–CD 3

C12H6D11NO MW: 202.34

D D

142.1

0 50

200 CD 3

106.1 D

100

C12H8D9NO MW: 200.32

140.1

100 64.1


CD 3

107.1

0

Relative Int. (%)

C12H9D8NO MW: 199.32

139.1

100 65.1


CD 3

107.1

0

Relative Int. (%)

200

I-2-B-vi

150 107.1 D

D

50 D

98.1

200 CD 3


NCOCH3 CD 2 –CD–CD 3

C12H3D14NO MW: 205.35

D D

145.1

0 50

100

150 m/z



200

250

59

Figure I-2. (Continued)

Relative Int. (%)

100

202.0

I-2-C-i 50

CH 3

Methamphetamine, trichloroacetyl derivative C12H14Cl3NO MW: 294.60

NCOCCl 3 CH 2 –CH–CH 3

91.1 118.1

0 50

100

150

Relative Int. (%)

100

200

250

206.0

I-2-C-ii

300 CD 3

D

NCOCCl 3

C12H9D5Cl3NO MW: 299.63

CH–CD–CH 3

50 92.1

350

Methamphetamine-d5, trichloroacetyl derivative

119.0

0 50

100

150

Relative Int. (%)

100

200

250

209.0

I-2-C-iii

300 CD 3

D


NCOCCl 3

C12H6D8Cl3NO MW: 302.65

CH–CD–CD 3

50 93.1

350

122.1

0 50

100

150

Relative Int. (%)

100

200

250

209.0

CD 3

I-2-C-iv 50

300

350


NCOCCl 3 CD 2 –CD–CD 3

C12H5D9Cl3NO MW: 303.66

93.1 123.1

0 50

100

150

Relative Int. (%)

100

200

250

208.0

CD 3

I-2-C-v D

D

50 96.1

D

126.1

300

350


NCOCCl 3 CH 2 –CH–CD 3

C12H3D11Cl3NO MW: 305.67

D D

0 50

100

150

Relative Int. (%)

100

200

250

209.0

CD 3

I-2-C-vi 50

D

98.1

D

128.2

300

D

350


NCOCCl 3 CD 2 –CD–CD 3

C12D14Cl3NO MW: 308.69

D D

0 50

100

150

200 m/z



250

300

350

60


Relative Int. (%)

100

154.1

I-2-D-i

CH 3 NCOCF3 CH 2 –CH–CH 3

50 91.1

110.0

Methamphetamine, trifluoroacetyl derivative

118.1

C12H14F3NO MW: 245.24

0 50

100

150

Relative Int. (%)

100

200 158.1

250 CD 3

I-2-D-ii

D

NCOCF3

Methamphetamine-d5, trifluoroacetyl derivative C12H9D5F3NO MW: 250.27

CH–CD–CH 3

50 113.1

300

120.1

92.1

0 50

100

150

Relative Int. (%)

100

200 161.1

I-2-D-iii

250 CD 3

D

NCOCF3

Methamphetamine-d8, trifluoroacetyl derivative C12H6D8F3NO MW: 253.29

CH–CD–CD 3

50 113.1 92.1

300

123.1

0 50

100

150

Relative Int. (%)

100

200

250

161.1

I-2-D-iv

CD 3

Methamphetamine-d9, trifluoroacetyl derivative

NCOCF3 CD 2 –CD–CD 3

50 113.1

300

C12H5D9F3NO MW: 254.30

123.1

93.1

0 50

100

150

Relative Int. (%)

100

200 160.1

CD 3

I-2-D-v D

50 113.1

126.1

250

D

96.1

NCOCF3

D

300

Methamphetamine-d11, trifluoroacetyl derivative

CH 2 –CH–CD 3

C12H3D11F3NO MW: 256.31

D D

0 50

100

150

Relative Int. (%)

100

200 161.1

I-2-D-vi

CD 3 D

50 98.1

113.1

128.2

250

D

D

NCOCF3

300

Methamphetamine-d14, trifluoroacetyl derivative C12D14F3NO MW: 259.33

CD 2 –CD–CD 3 D

D

0 50

100

150

200 m/z



250

300

61


Relative Int. (%)

100

204.1

CH 3

I-2-E-i

NCOC 2F 5

Methamphetamine, pentafluoropropionyl derivative C13H14F5NO MW: 295.25

CH 2 –CH–CH 3

50

91.1

160.0

118.1

0 50

100

150

200

Relative Int. (%)

100

208.1

CD 3 D

50

250

I-2-E-ii

NCOC 2F 5

300

350

Methamphetamine-d5, pentafluoropropionyl derivative C13H9D5F5NO MW: 300.28

CH–CD–CH 3

163.1

119.1 92.1

0 50

100

Relative Int. (%)

100

150

200 211.1

CD 3 D

NCOC 2F 5 CH–CD–CD 3

50

250

I-2-E-iii

300

350


163.1 92.1

123.1

0 50

100

150

200

Relative Int. (%)

100

211.1

CD 3

250

I-2-E-iv

NCOC 2F 5

300


CD 2 –CD–CD 3

50

350

163.1

123.1 93.1

0 50

100

Relative Int. (%)

100

150

200 210.1

CD 3 D

50

D

250

I-2-E-v

NCOC 2F 5

D

300


CH 2 –CH–CD 3

163.1

126.2

D D

350

96.1

0 50

100

Relative Int. (%)

100

150

200 211.1

CD 3 D

50

D

D

NCOC 2F 5

I-2-E-vi

300

98.1

350

Methamphetamine-d14, pentafluoropropionyl derivative C13D14F5NO MW: 309.33

CD 2 –CD–CD 3 D

D

250

163.1

128.2

0 50

100

150

200 m/z



250

300

350

62


Relative Int. (%)

100

254.1

CH 3

I-2-F-i

Methamphetamine, heptafluorobutyryl derivative

NCOC 3F 7

C14H14F7NO MW: 345.26

CH 2 –CH–CH 3

50 91.1

210.0

118.1

0 50

100

150

200

250

Relative Int. (%)

100

I-2-F-ii

258.1

CD 3 D

50

300

350

400

Methamphetamine-d5, heptafluorobutyryl derivative

NCOC 3F 7

C14H9D5F7NO MW: 350.29

CH–CD–CH 3

213.1 92.1

119.1

0 50

100

150

200

Relative Int. (%)

100

250 261.1

CD 3

I-2-F-iii

D

300

350

400


NCOC 3F 7

C14H6D8F7NO MW: 353.30

CH–CD–CD 3

50

213.1 92.1

123.1

0 50

100

150

200

250

Relative Int. (%)

100

I-2-F-iv

300 261.1

CD 3

350


NCOC 3F 7

C14H5D9F7NO MW: 354.31

CD 2 –CD–CD 3

50 93.1

400

213.1

123.1

0 50

100

150

200

Relative Int. (%)

100

250 260.1

CD 3

I-2-F-v D

126.2 D

400

C14H3D11F7NO MW: 356.32

CH 2 –CH–CD 3

213.1

D

350


NCOC 3F 7

D

50 96.1

300

D

0 50

100

150

200

Relative Int. (%)

100

D

98.1

128.2 D

D

300 261.1

CD 3

I-2-F-vi 50

250

350

400


NCOC 3F 7

C14D14F7NO MW: 359.34

CD 2 –CD–CD 3

213.1

D D

0 50

100

150

200

250 m/z



300

350

400

63


Relative Int. (%)

100

I-2-G-i

308.1

CH 3

Methamphetamine, 4-carboethoxyhexafluorobutyryl derivative

NCO(CF2)3COOC2H5 CH 2 –CH–CH 3

50 91.1

118.1

C17H19F6NO3 MW: 399.33 280.1

195.0

0 50

100

150

200

Relative Int. (%)

100

250

CD 3

I-2-G-ii

D

300 312.2

NCO(CF2)3COOC2H5

350

92.1

119.1

450

Methamphetamine-d5, 4-carboethoxyhexafluorobutyryl derivative C17H14D5F6NO3 MW: 404.36

CH–CD–CH 3

50

400

284.1

195.0

0 50

100

150

200

Relative Int. (%)

100

250

315.2

CD 3

I-2-G-iii

D

300

NCO(CF2)3COOC2H5

350

93.1

C17H11D8F6NO3 MW: 407.38 287.1

195.0

123.1

450

Methamphetamine-d8, 4-carboethoxyhexafluorobutyryl derivative

CH–CD–CD 3

50

400

0 50

100

150

200

250

Relative Int. (%)

100

315.2

CD 3

I-2-G-iv

300

350

93.1

123.1

450


NCO(CF2)3COOC2H5 CD 2 –CD–CD 3

50

400

C17H10D9F6NO3 MW: 408.38 287.1

195.0

0 50

100

150

200

250

Relative Int. (%)

100

D

50 97.1

314.2

CD 3

I-2-G-v 126.1

D

D

300

350

D

195.0

450


NCO(CF2)3COOC2H5 CH 2 –CH–CD 3

D

400

C17H8D11F6NO3 MW: 410.39 286.1

0 50

100

150

200

250

Relative Int. (%)

100

I-2-G-vi D

98.1

315.2

CD 3

50 128.2

D

D

350

400

450


NCO(CF2)3COOC2H5 CD 2 –CD–CD 3 D

D

300

C17H5D14F6NO3 MW: 413.41 287.1

195.0

0 50

100

150

200

250 m/z



300

350

400

450

64


Relative Int. (%)

100

195.0

CH 3

252.0

I-2-H-i

NCOC 6F 5

Methamphetamine, 2,3,4,5,6pentafluorobenzoyl derivative C17H14F5NO MW: 343.30

CH 2 –CH–CH 3

50

167.0

0 50

100

150

200

Relative Int. (%)

100

195.0

CD 3

D

250

300

256.0

I-2-H-ii

NCOC 6F 5

350

400

Methamphetamine-d5, 2,3,4,5,6pentafluorobenzoyl derivative C17H9D5F5NO MW: 348.26

CH–CD–CH 3

50

167.0

0 50

100

150

Relative Int. (%)

100

200

CD 3 D

250

195.0

259.1

NCOC 6F 5

300

I-2-H-iii

350

Methamphetamine-d8, 2,3,4,5,6pentafluorobenzoyl derivative

CH–CD–CD 3

50

400

C17H6D8F5NO MW: 351.24 167.0

0 50

100

150

200

Relative Int. (%)

100

250

195.0

CD 3

259.1

300

I-2-H-iv

NCOC 6F 5

350


CD 2 –CD–CD 3

50

400

167.0

0 50

100

150

Relative Int. (%)

100

200

CD 3 D

195.0

258.0

NCOC 6F 5

D

300

I-2-H-v

CH 2 –CH–CD 3

50 D

250

350

400


D D

167.0

0 50

100

150

200

Relative Int. (%)

100

195.0

CD 3 D

50

D

D

250 259.1

NCOC 6F 5

300

350

14, 2,3,4,5,6I-2-H-vi Methamphetamine-d pentafluorobenzoyl derivative

C17D14F5NO MW: 357.19

CD 2 –CD–CD 3

D

400

167.0

D

0 50

100

150

200

250 m/z



300

350

400

65


100

144.1

I-2-I-i 50

NCOOC3H7 CH 2 –CH–CH 3

58.1

176.1

50

100

150

Relative Int.(%)

100

200

148.1

50

D NCOOC3H7 CH–CD–CH 3

62.1 106.1

250 Methamphetamine-d5, propylformyl derivative

CD 3

I-2-I-ii

C14H16D5NO2 MW: 240.35

92.0 181.1

0 50

100


C14H21NO2 MW: 235.32

102.0

91.0

0

150

200 151.1

I-2-I-iii

D

NCOOC3H7 CH–CD–CD 3

65.1

50

250 Methamphetamine-d8, propylformyl derivative

CD 3

C14H13D8NO2 MW: 243,37

109.1 92.0 184.1

0 50

100

150


Methamphetamine, propylformyl derivative

CH 3

200 151.1

I-2-I-iv 50

Methamphetamine-d9, propylformyl derivative

CD 3 NCOOC3H7 CD 2 –CD–CD 3

65.1 93.0

250

109.1

C14H12D9NO2 MW: 244.38

185.1

0 50

100

150

Relative Int. (%)

100

200

150.1

CD 3

I-2-I-v D

D

CH 2 –CH–CD 3

64.1

50

108.1

D

96.1

NCOOC3H7

Methamphetamine-d11, propylformyl derivative C14H10D11NO2 MW: 246.39

D D

187.2

0 50

100

150


250

151.1

I-2-I-vi 65.1

50

200

D

98.1

0 100

150 m/z



NCOOC3H7 CD 2 –CD–CD 3

C14H7D14NO2 MW: 249.41

109.1 D

50

Methamphetamine-d14, propylformyl derivative

CD 3 D

250

D D

190.2

200

250

66


Relative Int. (%)

100

l-Methamphetamine, (S)-(–)-N(trifluoroacetyl)-prolyl derivative

166.0

I-2-J-i

H 3C O N C

58.1

50

N

CH 2 CH O CCF 3 CH 3

91.0

C17H21F3N2O2 MW: 342.36

251.1

119.1

0 50

100

150

Relative Int. (%)

100

200

250

300

166.0 D 3C

I-2-J-ii

D

62.1

50

O

N C

N

CH CD

400

C17H16D5F3N2O2 MW: 347.19

255.1

O CCF 3

CH 3

92.0

350

l-Methamphetamine-d5, (S)-(–)-N(trifluoroacetyl)-prolyl derivative

121.1

0 50

100

150

Relative Int. (%)

100

200 166.0

I-2-J-iii

250

300

D 3C O N C N CH CD O CCF 3 CD 3

50 93.0

400

C17H13D8F3N2O2 MW: 350.40

D

65.1

350

l-Methamphetamine-d8, (S)-(–)-N(trifluoroacetyl)-prolyl derivative 258.1

124.1

0 50

100

Relative Int. (%)

100

150

200

300

D 3C O N C

65.1

N

400

C17H12D9F3N2O2 MW: 351.41

258.1

CD 2 CD O CCF 3 CD 3

93.0

350


166.0

I-2-J-iv

50

250

125.1

0 50

100

Relative Int. (%)

100

150 166.0

I-2-J-v 64.1

50

200

D D

97.1 127.1

250

300

D 3C N

D

400

C17H10D11F3N2O2 MW: 353.42

O

CH 2 CH C CD 3

D

350

l-Methamphetamine-d11, (S)-(–)-N(trifluoroacetyl)-prolyl derivative 257.1

N O CCF 3

D

0 50

100

150

Relative Int. (%)

100

166.0

I-2-J-vi

D

65.1

50

200

D

D

300

N O CD 2 CD C D

350

400


D 3C

98.1 130.1

250

CD 3

258.1

C17H7D14F3N2O2 MW: 356.44

N

O CCF 3

D

0 50

100

150

200

250 m/z



300

350

400

67


Relative Int. (%)

100

I-2-K-i

H 3C O

166.0

N C

CH 2 CH O CCF 3 CH 3 251.1

58.1

50

d-Methamphetamine, (S)-(–)-N(trifluoroacetyl)-prolyl derivative

N

C17H21F3N2O2 MW: 342.36

91.0

0 50

100

Relative Int. (%)

100

I-2-K-ii

150

200

166.0

D 3C D

62.1

50

250

N C CH 3

350

400

d-Methamphetamine-d5, (S)-(–)-N(trifluoroacetyl)-prolyl derivative

O

CH CD

92.0

300

N O CCF 3

C17H16D5F3N2O2 MW: 347.19

255.1

0 50

100

Relative Int. (%)

100

I-2-K-iii

150

200

166.0

300

350

400


D 3C O

D

N C

N CH CD O CCF 3 CD 3

65.1

50

250

C17H13D8F3N2O2 MW: 350.40

258.1

93.0

0 50

100

Relative Int (%)

100

I-2-K-iv

150

200

166.0

300

N C N CD 2 CD O CCF 3 CD 3

93.0

350

400


D 3C O

65.1

50

250

C17H12D9F3N2O2 MW: 351.41

258.1

0 50

100

Relative Int. (%)

100

I-2-K-v

150 166.0

D

97.1

250

300

N

D

O

400

CD 3

C17H10D11F3N2O2 MW: 353.42

257.1

CH 2 CH C D

350


D 3C D

64.1

50

200

N O CCF 3

D

0 50

100

Relative Int. (%)

100

I-2-K-vi

150 166.0

98.1

250

300

D 3C D

65.1

50

200

D

N

D

D

CD 3

400


O

CD 2 CD C

350

C17H7D14F3N2O2 MW: 356.44

258.1

N O CCF 3

D

0 50

100

150

200

250 m/z



300

350

400

68


Relative Int. (%)

100

189.0

CH 3 NCOC(CF3)(C6H5)OCH3

274.1

CH 2 –CH–CH 3

50

l-Methamphetamine, (–)-α-methoxy-α-trifluoromethylphenylacetyl derivative

I-2-L-i

C20H22F3NO2 MW: 365.39

91.0

0 50

100

Relative Int. (%)

100

150

250

I-2-L-ii

NCOC(CF3)(C6H5)OCH3

278.1

CH–CD–CH 3

50

300

189.0

CD 3 D

200

350

400

l-Methamphetamine-d5, (–)-α-methoxy-α-trifluoromethylphenylacetyl derivative C20H17D5F3NO2 MW: 370.42

93.1

0 50

100

Relative Int. (%)

100

150

CD 3

D

200 189.0

NCOC(CF3)(C6H5)OCH3

250

I-2-L-iii 281.1

CH–CD–CD 3

50

300

350

400

l-Methamphetamine-d8, (–)-α-methoxy-α-trifluoromethylphenylacetyl derivative C20H14D8F3NO2 MW: 373.44

93.1

0 50

100

150

Relative Int. (%)

100

200

250

300

189.0

CD 3

I-2-L-iv

NCOC(CF3)(C6H5)OCH3

281.1

350

l-Methamphetamine-d9, (–)-α-methoxy-α-trifluoromethylphenylacetyl derivative

CD 2 –CD–CD 3

50

400

C20H13D9F3NO2 MW: 374.44

93.1

0 50

100

Relative Int. (%)

100

150

50

D

300

280.1

CH 2 –CH–CD 3

350

400


I-2-L-v

NCOC(CF3)(C6H5)OCH3

D

250

189.0

CD 3 D

200

C20H11D11F3NO2 MW: 376.46

D

97.1

D

0 50

100

Relative Int. (%)

100

150

189.0

CD 3 D

50

D

D

200

NCOC(CF3)(C6H5)OCH3

250

300

I-2-L-vi 281.1

350


CD 2 –CD–CD 3 D

C20H8D14F3NO2 MW: 379.47

98.1

D

400

98.1

0 50

100

150

200

250 m/z



300

350

400

69


Relative Int. (%)

100

CH 3

189.0

NCOC(CF3)(C6H5)OCH3

274.1

CH 2 –CH–CH 3

50

d-Methamphetamine, (–)-α-methoxy-α-trifluoromethylphenylacetyl derivative

I-2-M-i

C20H22F3NO2 MW: 365.39

91.0 119.0

0 50

100

Relative Int. (%)

100

150

189.0

CD 3 D

200

NCOC(CF3)(C6H5)OCH3

250

300

I-2-M-ii 278.1

CH–CD–CH 3

50

92.1

350

400

d-Methamphetamine-d5, (–)-α-methoxy-α-trifluoromethylphenylacetyl derivative C20H17D5F3NO2 MW: 370.42

121.1

0 50

100

Relative Int. (%)

100

150

CD 3

D

200 189.0

NCOC(CF3)(C6H5)OCH3

250

I-2-M-iii

300

281.1

93.1

400

C20H14D8F3NO2 MW: 373.44

CH–CD–CD 3

50

350

d-Methamphetamine-d8, (–)-α-methoxy-α-trifluoromethylphenylacetyl derivative

124.1

0 50

100

150

Relative Int. (%)

100

200

250

300

189.0

CD 3

I-2-M-iv

NCOC(CF3)(C6H5)OCH3

281.1

400

C20H13D9F3NO2 MW: 374.44

CD 2 –CD–CD 3

50

350

d-Methamphetamine-d9, (–)-α-methoxy-α-trifluoromethylphenylacetyl derivative

93.1 125.1

0 50

100

150

Relative Int. (%)

100

200 189.0

CD 3

50

D D

250

I-2-M-v 280.1

NCOC(CF3)(C6H5)OCH3

D

300

D

97.1

400


CH 2 –CH–CD 3 D

350

127.1

0 50

100

Relative Int. (%)

100

150

50

D

D

250

300

189.0

CD 3 D

200

I-2-M-vi

NCOC(CF3)(C6H5)OCH3

281.1

CD 2 –CD–CD 3 D

400


98.1

D

350

130.1

0 50

100

150

200

250 m/z



300

350

400

70


Relative Int. (%)

100

I-2-N-i

50

CH 3

NSi(CH3)3 CH 2 –CH–CH 3

73.1 58.1

Methamphetamine, trimethylsilyl derivative

130.1

C13H23NSi MW: 221.41

91.1

206.2

0 50

100

150

Relative Int. (%)

100

200

134.2

50

D

NSi(CH3)3 CH–CD–CH 3

73.1 62.1

Methamphetamine-d5, trimethylsilyl derivative

CD 3

I-2-N-ii

250

C13H18D5NSi MW: 226.44

92.1

211.2

0 50

100

150

Relative Int. (%)

100

I-2-N-iii 50

200

137.2

250 Methamphetamine-d8, trimethylsilyl derivative

CD 3 D

NSi(CH3)3 CH–CD–CD 3

C13H15D8NSi MW: 229.46

73.1 65.2

214.2

92.1

0 50

100

150

Relative Int.(%)

100

200

137.2

CD 3

I-2-N-iv


NSi(CH3)3 CD 2 –CD–CD 3

50

C13H14D9NSi MW: 230.47

73.1 65.2

93.1

215.2

0 50

100

150

Relative Int. (%)

100

I-2-N-v

136.2 D


CD 3 D

50

200

NSi(CH3)3 CH 2 –CH–CD 3

C13H12D11NSi MW: 232.48

73.1 D

64.2

96.2

D D

217.2

0 50

100

150

Relative Int. (%)

100

200

137.2

CD 3

I-2-N-vi D

50

D


NSi(CH3)3 CD 2 –CD–CD 3

C13H9D14NSi MW: 235.50

73.1 65.2

98.2

D

D D

220.3

0 50

100

150 m/z



200

250

71


Relative Int. (%)

100

172.1

CH 3 NSi(CH3)2C(CH ) 3 3 CH 2 –CH–CH 3

73.1 75.1

50

Methamphetamine, t-butyldimethylsilyl derivative

I-2-O-i

C16H29NSi MW: 263.49

147.1 206.1 248.1

0 50

100

150

Relative Int.(%)

100

200 176.2

CD 3 NSi(CH3)2C(CH3)3 CH–CD–CH 3

D

50

73.1

75.1

250

300

Methamphetamine-d5, t-butyldimethylsilyl derivative

I-2-O-ii

C16H24D5NSi MW: 268.52 211.2

149.0

253.1

0 50

100

150

Relative Int. (%)

100

CD 3

D

50

73.1

200 179.2

250

300


I-2-O-iii

NSi(CH3)2C(CH3)3

C16H21D8NSi MW: 271.54

CH–CD–CD 3

75.1

214.2 149.0

256.2

0 50

100

150

Relative Int. (%)

100 CD 3

50

73.1

200

300


I-2-O-iv


75.1

250

179.2

C16H20D9NSi MW: 272.55 215.2

149.0

257.1

0 50

100

Relative Int. (%)

100 73.1

150

D

50

178.2

CD 3

75.1

D

D

200

NSi(CH3)2C(CH3)3 CH 2 –CH–CD 3

300


I-2-O-v

C16H18D11NSi MW: 274.56

149.0

D

250

217.2

D

258.1

0 50

100

150

Relative Int. (%)

100

50

75.1

D D

D

300


I-2-O-vi

NSi(CH3)2C(CH ) 3 3 CD 2 –CD–CD 3 D

D

250

179.2

CD 3

73.1

200

C16H15D14NSi MW: 277.58 220.2

149.0

262.3

0 50

100

150

200 m/z



250

300

72

Figure I-3. Mass spectra of ephedrine and its deuterated analog (ephedrine-d3): (A) underivatized; (B) acetylderivatized; (C) TCA-derivatized; (D) [TFA]2-derivatized; (E) [PFP]2-derivatized; (F) [HFB]2-derivatized; (G) 4-CBderivatized; (H) PFB-derivatized; (I) propylformyl-derivatized; (J) d-TPC-derivatized; (K) d-MTPA-derivatized; (L) [TMS]2-derivatized. Relative Int. (%)

100

58.0

I-3-A-i

Ephedrine C10H15NO MW: 165.23

CH 3 CH–CH–NH–CH 3

50

OH

77.0

0 50

100

Relative Int. (%)

100

61.1

150

200 Ephedrine-d3

I-3-A-ii

CH 3

C10H12D3NO MW: 168.25

CH–CH–NH–CD 3

50

OH

77.0

0 50

100

150

200

m/z Relative Int. (%)

100

58.1

I-3-B-i

Ephedrine, acetyl derivative

COCH 3

100.1

CH–CH–N–CH 3

50

C12H17NO2 MW: 207.27

OH CH 3

77.1

0 50

100

Relative Int. (%)

100

61.1

150

I-3-B-ii

200

250 Ephedrine-d3, acetyl derivative

COCH 3

103.1

CH–CH–N–CD 3

50

C12H14D3NO2 MW: 210.29

OH CH 3

77.1

0 50

100

Relative Int. (%)

100

150 m/z

200

Ephedrine, trichloroacetyl derivative

201.9

I-3-C-i

COCCl 3 CH–CH–N–CH 3

50 117.0 56.0

250

C12H14Cl3NO2 MW: 310.60

OH CH 3

91.0

0 50

100

Relative Int. (%)

100

150

I-3-C-ii

200

250

350

Ephedrine-d3, trichloroacetyl derivative

204.9

COCCl 3 CH–CH–N–CD 3

50 117.0 59.0

300

C12H11D3Cl3NO2 MW: 313.62

OH CH 3

91.0

0 50

100

150

200 m/z



250

300

350

73


Relative Int. (%)

100

154.1

I-3-D-i

50

O

COCF 3

110.0 69.0

50

C14H13F6NO3 MW: 357.25

CH 3

244.1

0 100

150


Ephedrine, di-trifluoroacetyl derivative

COCF 3 CH–CH–N–CH 3

200

250

300

157.1

I-3-D-ii

350

Ephedrine-d3, di-trifluoroacetyl derivative

COCF 3 CH–CH–N–CD 3

50

O

113.1

C14H10D3F6NO3 MW: 360.27

CH 3

COCF 3

69.1

247.1

0 50

400

100

150

200

250

300

350

400


100

204.1

I-3-E-i

CH–CH–N–CH 3

50

O

160.1

50

100

294.1

150

200

100

250

300

207.1

I-3-E-ii

O

400

450

500

Ephedrine-d3, di-pentafluoropropionyl derivative C16H10D3F10NO3 MW: 460.28

CH 3

COC 2 F 5

163.1 119.0

297.1

0 100

350

COC 2 F 5 CH–CH–N–CD 3

50

50

C16H13F10NO3 MW: 457.26

CH 3

COC 2 F 5

119.0

0

Relative Int. (%)

Ephedrine, di-pentafluoropropionyl derivative

COC 2 F 5

150

200

250

300

350

400

450

500


100

254.1

I-3-F-i

CH–CH–N–CH 3 O

50 69.1

50 100

100

150

200

C18H13F14NO3 MW: 557.28

CH 3

COC 3 F 7

210.0 169.0

344.1

0

Relative Int. (%)

Ephedrine, di-heptafluorobutyryl derivative

COC 3 F 7

250

300

350

400

450

257.1

I-3-F-ii

500

CH–CH–N–CD 3 O

213.1

347.1

0 50

100

150

200

250

300

350 m/z



C18H10D3F14NO3 MW: 560.30

CH 3

COC 3 F 7

169.0

69.1

600

Ephedrine-d3, di-heptafluorobutyryl derivative

COC 3 F 7

50

550

400

450

500

550

600

74


Relative Int. (%)

100

308.1

I-3-G-i

Ephedrine, 4-carboethoxyhexafluorobutyryl derivative

CO(CF2)3COOC2H 5

CH–CH–N–CH 3

50

C17H19F6NO4 MW: 415.33

OH CH 3

86.1

195.0

136.1

280.1

262.0

370.1


100

100

150

200

250

300

350 311.1

I-3-G-ii

CH–CH–N–CD 3

50

C17H16D3F6NO4 MW: 418.35

OH CH 3

89.1

139.1

147.1

50

100

100

150

450

Ephedrine-d3, 4-carboethoxyhexafluorobutyryl derivative

CO(CF2)3COOC2H 5

195.0

283.1

265.1

373.2

0

Relative Int. (%)

400

200

250 m/z

300

350

195.0

I-3-H-i

400

450

Ephedrine, 2,3,4,5,6-pentafluorobenzoyl derivative

252.0

COC 6 F 5 CH–CH–N–CH 3

50 167.0

C17H14F5NO2 MW: 359.29

OH CH 3


100

100

150

200

250

195.0

I-3-H-ii

300

350

400

Ephedrine-d3, 2,3,4,5,6-pentafluorobutyryl derivative

255.0

COC 6 F 5 CH–CH–N–CD 3

50

C17H11D3F5NO2 MW: 362.31

OH CH 3

167.0

0 50

100

150

200

250

300

350

400


100

144.1

I-3-I-i

Ephedrine, propylformyl derivative COOC 3H 7 CH–CH–N–CH 3

58.1

50

102.0

C14H21NO3 MW: 251.31

OH CH 3

77.0

0 50

100

150

Relative Int. (%)

100

200

147.1

I-3-I-ii 61.1

50

COOC 3H 7 CH–CH–N–CD 3

105.0

250

300

Ephedrine-d3, propylformyl derivative C14H18D3NO3 MW: 254.29

OH CH 3

77.0

0 50

100

150

200 m/z



250

300

75


100

166.0

CH 3

CH CH

N CH 3 O CCF 3

OH

50 69.1 96.1

d-Ephedrine, (S)-(–)-N-(trifluoroacetyl)-prolyl derivative

O N C

C17H21F3N2O3 MW: 358.36

I-3-J-i

251.1

194.1

0 50

100

150

Relative Int. (%)

100

200

250

166.1

61.1 69.1

N CD 3 O CCF 3

400

C17H18D3F3N2O3 MW: 361.37

I-3-J-ii

254.1 96.0

350

d-Ephedrine-d3, (S)-(–)-N-(trifluoroacetyl)-prolyl derivative

CH 3 O CH CH N C OH

50

300

194.0

0 50

100

150

200

250

300

350

400


100

COC(CF3)(C6H5)OCH3

189.0

d-Ephedrine, (–)-α-methoxy− α−trifluoromethylphenylacetyl derivative

CH–CH–N–CH 3 OH CH 3

50 77.0

274.1

C20H22F3NO3 MW: 381.39

I-3-K-i

98.1

141.1

305.2

200.0

0 50

100

150

Relative Int. (%)

100

200

250

300

189.0 CH–CH–N–CD 3

277.1

OH CH 3

77.0

98.1

I-3-K-ii 141.1

400

d-Ephedrine-d3, (–)-α-methoxy− α−trifluoromethylphenylacetyl derivative

COC(CF3)(C6H5)OCH3

50

350

C20H19D3F3NO3 MW: 384.41

305.2

203.0

0 50

100

150

200

250

300

350

400

m/z Relative Int.(%)

100

130.2

Ephedrine, di-trimethylsilyl derivative

Si(CH3)3 CH–CH–N–CH 3 O CH 3

50 73.1

C16H31NOSi2 MW: 309.59

I-3-L-i

Si(CH3)3

0 50

100

Relative Int. (%)

100

150

200

250

300

133.2

350

Ephedrine-d3, di-trimethylsilyl derivative

Si(CH3)3 CH–CH–N–CD 3

50

O

73.1

400

CH 3

I-3-L-ii

Si(CH3)3

C16H28D3NOSi2 MW: 312.61

0 50

100

150

200

250 m/z



300

350

400

76

Figure I-4. Mass spectra of phenylpropanolamine (PPA) and its deuterated analog (PPA-d3): (A) underivatized; (B) acetyl-derivatized; (C) TCA-derivatized; (D) [TFA]2-derivatized; (E) [PFP]2-derivatized; (F) [HFB]2-derivatized; (G) 4-CB-derivatized; (H) PFB-derivatized; (I,J) l-TPC-derivatized; (K,L) l-MTPA-derivatized; (M) [TMS]2-derivatized; (N) t-BDMS-derivatized; (O) [t-BDMS]2-derivatized; (P) TFA/[t-BDMS]2-derivatized; (Q) PFP/[t-BDMS]2-derivatized; (R) HFB/[t-BDMS]2-derivatized. Relative Int. (%)

100

44.0

I-4-A-i

Phenylpropanolamine C9H13NO MW: 151.21

OH CH 3

50

NH2

77.0


100

90 47.1

140

I-4-A-ii

190 Phenylpropanolamine-d3

OH

C9H10D3NO MW: 154.22

CD 3 NH2

50 77.0

0 40

90

140

190

m/z

Relative Int. (%)

100

44.1

OH

86.1

I-4-B-i

Phenylpropanolamine, acetyl derivative

CH 3 NH

C11H15NO2 MW: 193.24

COCH 3

50 69.1

107.0

134.1

176.0


100

90 47.1

140

190 OH

I-4-B-ii

CD 3

89.1

Phenylpropanolamine-d3, acetyl derivative

NH

C11H12D3NO2 MW: 196.26

COCH 3

50 72.1

107.0

137.1

179.1

0 40

90

140

190


100

Phenylpropanolamine, trichloroacetyl derivative

187.9

I-4-C-i

OH CH 3

50

C11H12Cl3NO2 MW: 296.58

NH

117.0

COCCl 3

160.0

277.9

77.0

0 50 relative Int. (%)

100

100

150

200

250

Phenylpropanolamine-d3, trichloroacetyl derivative

190.9

I-4-C-ii

OH CD 3

50

C11H9D3Cl3NO2 MW: 299.59

NH

118.9

COCCl 3

163.0

300

280.9

77.0

0 50

100

150

200 m/z



250

300

77


Relative Int. (%)

100

140.1

I-4-D-i

O

Phenylpropanolamine, di-trifluoroacetyl derivative

COCF 3 CH 3

50

C13H11F6NO3 MW: 343.22

N COCF 3 H

69.1

105.1

230.1 203.1

0 50

100

150

Relative Int. (%)

100

200

143.1

I-4-D-ii

O

250

COCF 3 CD 3

N COCF 3 H

50 69.1

300

105.1

350

Phenylpropanolamine-d3, di-trifluoroacetyl derivative C13H8D3F6NO3 MW: 346.24

233.1 203.1

175.1

0 50

100

Relative Int. (%)

100

150

200 m/z

250

300

190.1

I-4-E-i

Phenylpropanolamine, di-pentafluoropropionyl derivative

OCOC 2F 5 CH 3

50

N COC 2 F 5

119.0

105.1

225.1

253.1

C15H11F10NO3 MW: 443.24

H

280.1

350

0 50

100

Relative Int. (%)

100

150

200

300

350

400

193.1

1-4-E-ii

50

250

N

283.1

COC 2 F 5

C15H8D3F10NO3 MW: 446.25

H

253.1

105.1

500

Phenylpropanolamine-d3, di-pentafluoropropionyl derivative

OCOC 2F 5 CD 3

119.1

450

225.1

0 50

100

150

200

250

300

350

400

450

500


100

240.1

I-4-F-i

Phenylpropanolamine, di-heptafluorobutyryl derivative OCOC 3F 7 CH 3

50 69.0

169.0

105.1

275.0

330.1

303.0

C17H11F14NO3 MW: 543.25

N COC 3 F 7 H

0 50

100

150

200

Relative Int. (%)

100

250

300

350

400

I-4-F-ii 50

OCOC 3F 7 CD 3

333.1 169.1 69.1

450

243.1

550

600

Phenylpropanolamine-d3, di-heptafluorobutyryl derivative C17H8D3F14NO3 MW: 546.27

N COC 3 F 7 H

275.1 303.1

105.1

500

0 50

100

150

200

250

300

350 m/z



400

450

500

550

600

78


Relative Int. (%)

100

I-4-G-i

294.0

OH

Phenylpropanolamine, 4-carboethoxyhexafluorobutyryl derivative

CH 3 NH

50

CO(CF2)3COOC2H 5

117.1

195.0

C16H17F6NO4 MW: 401.30 384.1

266.0 248.0

338.0

0 50

100

150

200

250

300

Relative Int. (%)

100

350

297.0

I-4-G-ii

400

Phenylpropanolamine-d3, 4-carboethoxyhexafluorobutyryl derivative

OH CD 3 NH

50

CO(CF2)3COOC2H 5

119.0

C16H14D3F6NO4 MW: 404.32 387.1

269.0 250.0

195.0

450

341.0

0 50

100

150

200

relative Int. (%)

100

250 m/z

300

350

238.0

OH CH 3

50

C16H12F5NO2 MW: 345.26

NH COC 6 F 5

167.0

117.0

327.9

0 50

100

150

200

Relative Int. (%)

100

250

300

350

195.0

I-4-H-ii

241.0

CD 3

C16H9D3F5NO2 MW: 348.28

NH COC 6 F 5

167.0

117.0

400

Phenylpropanolamine-d3, 2,3,4,5,6-pentafluorobenzoyl derivative

OH

50

450

Phenylpropanolamine, 2,3,4,5,6-pentafluorobenzoyl derivative

195.0

I-4-H-i

400

331.0

0 50

100

150

200

250

300

350

400


100

166.1

HO

I-4-I-i

CH 3

l-Phenylpropanolamine, (S)-(–)-N-(trifluoroacetyl)-prolyl derivative

O

NH C

50

N

C16H19F3N2O3 MW: 344.33

O CCF 3

237.1

194.0

69.1

96.1

220.1

0 50

100

150

Relative Int. (%)

100

200

250

300

HO CD 3 O NH C

50 69.0

100

150

200

250 m/z



N O CCF 3

C16H16D3F3N2O3 MW: 347.35

223.1

0 50

240.1

194.0

96.0

400

l-Phenylpropanolamine-d3, (S)-(–)-N-(trifluoroacetyl)-prolyl derivative

166.1

I-4-I-ii

350

300

350

400

79


Relative Int. (%)

100

166.1

I-4-J-i

HO CH 3 O

50

NH C

194.1

69.1

96.0

237.1

d-Phenylpropanolamine, (S)-(–)-N-(trifluoroacetyl)-prolyl derivative C16H19F3N2O3 MW: 344.33

N

O CCF 3

220.1

0 50

100

150

Relative Int. (%)

100

200

250

300

350

166.1

I-4-J-ii

HO CD 3 O

50

NH C

194.0

69.1

96.0

223.1

240.1

400

d-Phenylpropanolamine-d3, (S)-(–)-N-(trifluoroacetyl)-prolyl derivative N

C16H16D3F3N2O3 MW: 347.35

O CCF 3

0 50

100

150

200

250

300

350

400


100

189.0

I-4-K-i 186.0

261.1

50 105.0 119.0 134.1

77.0

l-Phenylpropanolamine, (–)-α-methoxy-α-trifluoromethylphenylacetyl derivative CH 3 C19H20F3NO3 NH MW: 367.36

OH

229.0

160.1

COC(CF3)(C6H5)OCH3


100

100

150

200

250

300

I-4-K-ii

OH

186.0

CD 3

264.1

50

350

C19H17D3F3NO3 MW: 370.38

NH

105.0

77.0

119.0

137.1

232.1

163.1

400

l-Phenylpropanolamine-d3, (–)-α-methoxy-α-trifluoromethylphenylacetyl derivative

189.0

COC(CF3)(C6H5)OCH3

0 50

100

150

200

250

300

350

400


100

189.0

I-4-L-i

186.0

261.1

OH

CH 3

50 105.0

77.0

119.0 134.1

229.0 160.1

d-Phenylpropanolamine, (–)-α-methoxy-α-trifluoromethylphenylacetyl derivative C19H20F3NO3 MW: 367.36

NH COC(CF3)(C6H5)OCH3


100

100

150

200

250

300

189.0

I-4-L-ii

OH

186.0 264.1

50 77.0

137.1

232.0

163.1

400

d-Phenylpropanolamine-d3, (–)-α-methoxy-α-trifluoromethylphenylacetyl derivative CD 3

NH

105.0 119.0

350

C19H17D3F3NO3 MW: 370.38

COC(CF3)(C6H5)OCH3

0 50

100

150

200

250 m/z



300

350

400

80


100

116.1

I-4-M-i

Phenylpropanolamine, di-trimethylsilyl derivative

OSi(CH3)3 CH 3

50

C15H29NOSi2 MW: 295.57

N Si(CH3)3

73.1

H

147.1

179.1

280.2

0 50

100

150

Relative Int. (%)

100

200

250

119.2

I-4-M-ii

Phenylpropanolamine-d3, di-trimethylsilyl derivative

OSi(CH3)3 CD 3

73.2

N

50

300

C15H26D3NOSi2 MW: 298.59

Si(CH3)3

H

147.2

283.2

179.2

0 50

100

150

200

250

300


100

OH CH 3 Si(CH3)2C(CH3)3

134.1

50 100

208.1

149.1

0

Relative Int. (%)

C15H27NOSi MW: 265.47

NH

73.1

50

Phenylpropanolamine, t-butyldimethylsilyl derivative

158.1

I-4-N-i

100

150

200 161.3

I-4-N-ii

250

300

Phenylpropanolamine-d3, t-butyldimethylsilyl derivative

OH CD 3

C15H24D3NOSi MW: 268.48

NH

73.2

50

Si(CH3)2C(CH3)3

137.2

149.1

211.2

0 50

100

150

200

250

300


100

158.1

I-4-O-i

OSi(CH3)2C(CH3)3 CH 3 NH

50

73.1 147.0

50 100

C21H41NOSi2 MW: 379.73

Si(CH3)2C(CH3)3

322.1

0

Relative Int. (%)

Phenylpropanolamine, di-t-butyldimethylsilyl derivative

100

150

200

250

300

161.2

I-4-O-ii

OSi(CH3)2C(CH3)3 CD 3

73.1

350

Phenylpropanolamine-d3, di-t-butyldimethylsilyl derivative

NH

50

C21H38D3NOSi2 MW: 382.74

Si(CH3)2C(CH3)3

147.1

400

325.2

0 50

100

150

200

250 m/z



300

350

400

81


100

221.1

I-4-P-i

O CH 3

73.1

50

Phenylpropanolamine, trifluoroacetyl/di-t-butyldimethylsilyl derivative

Si(CH3)2C(CH3)3

N

115.1

COCF 3

C23H40F3NO2Si2 MW: 475.74

418.2

Si(CH3)2C(CH3)3

191.1

0 50

100

Relative Int. (%)

100

150

200

250

300

221.1

I-4-P-ii

350

O CD 3 N

500

C23H37D3F3NO2Si2 MW: 478.75

421.2

COCF 3

Si(CH3)2C(CH3)3

194.1

115.1

450

Phenylpropanolamine-d3, trifluoroacetyl/di-t-butyldimethylsilyl derivative

Si(CH3)2C(CH3)3

73.1

50

400

0 50

100

150

200

250

300

350

400

450

500


100

221.1

I-4-Q-i

Phenylpropanolamine, pentafluoropropionyl/di-t-butyldimethylsilyl derivative

Si(CH3)2C(CH3)3 O

73.0

CH 3

50

N

117.0

190.1

249.1

COC 2 F 5

Si(CH3)2C(CH3)3

304.1

C24H40F5NO2Si2 MW: 525.74

468.2

0 50

100

150

200

Relative Int. (%)

100

250

300

350

221.1 73.0

400

Si(CH3)2C(CH3)3

I-4-Q-ii

CD 3 N

115.1

252.1

194.0

COC 2 F 5

Si(CH3)2C(CH3)3

307.1

500

550

Phenylpropanolamine-d3, pentafluoropropionyl/di-t-butyldimethylsilyl derivative

O

50

450

471.2

C24H37D3F5NO2Si2 MW: 528.76

0 50

100

150

Relative Int. (%)

100

200

I-4-R-i

250

300 m/z

350

221.1

400

O

73.0

CH 3 N

115.1

249.1

550

C25H40F7NO2Si2 MW: 575.74

COC 3 F 7

518.2

Si(CH3)2C(CH3)3

354.1

500

Phenylpropanolamine, heptafluorobutyryl/di-t-butyldimethylsilyl derivative

Si(CH3)2C(CH3)3

50

450

0 50

100

Relative Int. (%)

100

150

200

I-4-R-ii

250

300

350

400

221.1

450

Si(CH3)2C(CH3)3

CD 3

73.0 N

357.1

252.1

115.0

550

600

Phenylpropanolamine-d3, heptafluorobutyryl/di-t-butyldimethylsilyl derivative

O

50

500

COC 3 F 7

521.2

Si(CH3)2C(CH3)3

C25H37D3F7NO2Si2 MW: 578.76

0 50

100

150

200

250

300

350 m/z



400

450

500

550

600

82

Figure I-5. Mass spectra of 3,4-methylenedioxyamphetamine (MDA) and its deuterated analog (MDA-d5): (A) underivatized; (B) acetyl-derivatized; (C) TCA-derivatized; (D) TFA-derivatized; (E) PFP-derivatized; (F) HFBderivatized; (G) 4-CB-derivatized; (H) PFB-derivatized; (I) propylformyl-derivatized; (J,K) l-TPC-derivatized; (L,M) l-MTPA-derivatized; (N) TMS-derivatized; (O) TFA/t-BDMS-derivatized; (P) PFP/t-BDMS-derivatized; (Q) HFB/tBDMS-derivatized Relative Int. (%)

100

44.1

I-5-A-i

CH 3 CH 2–CH–NH 2

O

MDA C10H13NO2 MW: 179.22

O

50

136.0 77.0


100

90 48.1

140

I-5-A-ii

D

50

190 MDA-d5

CD 3

O

CH–C–NH 2

O

D

C10H8D5NO2 MW: 184.25 137.0

78.0

0 40

90

140

190


100

I-5-B-i

CH 3 CH 2 –CH– NHCOCH

O

44.1

MDA, acetyl derivative

162.1

C12H15NO3 MW: 221.25

3

O

50

135.1 86.1

77.1

221.1


100

90 48.1

140 D

I-5-B-ii

CH–C– NHCOCH

O

D

O

50

190 167.1

CD 3

240 MDA-d5, acetyl derivative C12H10D5NO3 MW: 226.28

3

136.1

90.1

78.1

226.1

0 40

Relative Int. (%)

100

90

140 m/z 135.1

I-5-C-i

190

240

162.1

MDA, trichloroacetyl derivative

CH 3 O

50

C12H12Cl3NO3 MW: 324.59

CH 2 –CH– NHCOCCl3

O

77.1

188.0

105.1

323.0

0 50

100

150

Relative Int. (%)

100

200

250

136.1

I-5-C-ii

167.1

D

O

50

CD 3

350

MDA-d5, trichloroacetyl derivative C12H7D5Cl3NO3 MW: 329.62

CH–C– NHCOCCl3 D

O

78.1

300

192.0

110.1

328.1

0 50

100

150

200 m/z



250

300

350

83


100

135.1

I-5-D-i

MDA, trifluoroacetyl derivative

CH 3 CH 2 –CH–NHCOCF3

O

162.1

50

C12H12F3NO3 MW: 275.22

O

275.1

77.1

0 50

100

Relative Int. (%)

100

150

200

250

136.1

I-5-D-ii

D

MDA-d5, trifluoroacetyl derivative

CD 3

CH–C–NHCOCF3

O

50

300

C12H7D5F3NO3 MW: 280.25

D

O

167.1 78.1

280.1

144.1

0 50

100

150

200

250

300


100

MDA, pentafluoropropionyl derivative

135.1

I-5-E-i

162.1

50

O

CH 3 CH 2 –CH– NHCOC 2F5

C13H12F5NO3 MW: 325.23

O

77.1

119.0

325.1

190.0

0 50

100

150

Relative Int. (%)

100

200

250

I-5-E-ii

350

MDA-d5, pentafluoropropionyl derivative D

50

O

167.1 78.1

300

136.1

119.0

O

CD 3

C13H7D5F5NO3 MW: 330.26

CH–C– NHCOC 2F5 D

330.1

194.1

0 50

Relative Int. (%)

100

100

I-5-F-i

150

200 m/z

250

300

135.1 CH 3

162.1

O

50

350

MDA, heptafluorobutyryl derivative C14H12F7NO3 MW: 375.24

CH 2 –CH– NHCOC 3F7

O

77.1

375.1

240.0


100

100

I-5-F-ii

150

200

250

300

350

400

136.1 O

50

O

167.1

D CD 3 MDA-d5, heptafluorobutyryl derivative CH–C– NHCOC 3F7

C14H7D5F7NO3 MW: 380.27 380.1

D

244.1

69.1

0 50

100

150

200

250 m/z



300

350

400

84


100

MDA, 4-carboethoxyhexafluorobutyryl derivative

162.1

I-5-G-i

CH 3

135.1

O

266.1

248.0


100

100

150

200

250

300

350

136.1

I-5-G-ii

166.1

D

0 150

200

270.1

250 m/z

100

195.0 162.1

I-5-H-i

C17H12D5F6NO5 MW: 434.34

D

251.1

O

434.2

298.1

300

350

CH 3 CH 2 –CH– NHCOC 6F5

400

450

MDA, 2,3,4,5,6-pentafluorobenzoyl derivative C17H12F5NO3 MW: 373.27

O

50

450

MDA-d5, 4-carboethoxyhexafluorobutyryl derivative

CD 3

O

100

400

CH–C– NHCO(CF2)3COOC2H5

O

50

50

429.2

294.1

0

Relative Int. (%)

C17H17F6NO5 MW: 429.31

CH 2 –CH– NHCO(CF2)3COOC2H5

O

50

135.1 238.0

77.1

373.1


100

100

150

200

250

300

195.0

I-5-H-ii 167.1

50

D CD 3 CH–C– NHCOC 6F5

O

242.0

78.1

400

C17H7D5F5NO3 MW: 378.30

D

O

136.1

350

MDA-d5, 2,3,4,5,6-pentafluorobenzoyl derivative

378.1

0 50

100

150

200

250

300

350

400


100

130.1

I-5-I-i

MDA, propylformyl derivative

CH 3 CH 2 –CH–NHCOOC3H7

O

50

162.0 77.0

O

105.0

C14H19NO4 MW: 265.31 265.1

206.1


100

100

150

200

250

134.1

I-5-I-ii

D

167.1 78.0

MDA-d5, propylformyl derivative

CD 3

CH–C– NHCOOC3H7

O

50

D

O

106.0

300

C14H14D5NO4 MW: 270.34 270.2

211.1

0 50

100

150

200 m/z



250

300

85


100 162.0

I-5-J-i

166.0

CH 3 O

50

l-MDA, (S)-(–)-N-(trifluoroacetyl)-prolyl derivative

O

CH 2 CH NH C

N

C17H19F3N2O4 MW: 372.34

O CCF 3

O

194.0

135.0

237.1

372.1

0 50

100

150

Relative Int. (%)

100

200

250

166.0

I-5-J-ii

O

50

300

D CD 3 O CH C NH C D

O

350

C17H14D5F3N2O4 MW: 377.37

N

O CCF 3

194.0

136.0

241.1

377.2

0 50

100

400

l-MDA-d5, (S)-(–)-N-(trifluoroacetyl)-prolyl derivative

150

200

250

300

350

400


100

I-5-K-i

162.1

166.0 O

50

CH 3 O CH 2 CH NH C

d-MDA, (S)-(–)-N-(trifluoroacetyl)-prolyl derivative N

C17H19F3N2O4 MW: 372.34

O CCF 3

O

194.0

135.0

237.1

372.2

0 50

100

150

Relative Int. (%)

100

200

250

300

166.1

I-5-K-ii

D O

50

CD 3

D

O

136.0

194.0

400

d-MDA-d5, (S)-(–)-N-(trifluoroacetyl)-prolyl derivative

O

CH C NH C

350

N O CCF 3

C17H14D5F3N2O4 MW: 377.37

241.1

377.2

0 50

100

150

200

250

300

350

400


100

162.0

I-5-L-i

189.0

CH 3 O

50 105.0

77.0

l-MDA, (–)-α-methoxy-α-trifluoromethylphenylacetyl derivative C20H20F3NO4 MW: 395.37

CH 2 –CH– NHCOC(CF3)(C6H5)OCH3

O

135.0

206.0

260.0


100

100

150

200

250

189.0

I-5-L-ii

167.1

D O

50 105.0

CD 3

350

400

l-MDA-d5, (–)-α-methoxy-α-trifluoromethylphenylacetyl derivative

CH–C– NHCOC(CF3)(C6H5)OCH3 D

O

136.0 78.1

300

C20H15D5F3NO4 MW: 400.40

264.1

211.1

0 50

100

150

200

250 m/z



300

350

400

86


100

162.0

I-5-M-i

d-MDA, (–)-α-methoxy-α-trifluoromethylphenylacetyl derivative

189.0

50

CH 3 CH 2 –CH– NHCOC(CF3)(C6H5)OCH3

O

105.0

77.0

C20H20F3NO4 MW: 395.37

O

135.0 206.0

260.0

0 50

100

150

200

Relative Int. (%)

100

D

CD 3

211.1

400

d-MDA-d5, (–)-α-methoxy-α-trifluoromethylphenylacetyl derivative C20H15D5F3NO4 MW: 400.40

D

O

136.0 105.0

350

CH–C– NHCOC(CF3)(C6H5)OCH3

O

50 78.0

300

189.0

167.1

I-5-M-ii

250

264.1

0 50

100

150

200

250

300

350

400

m/z

Relative Int. (%)

100

116.2

I-5-N-i

O

50

MDA, trimethylsilyl derivative

CH 3 CH 2 –CH– NHSi(CH3)3

C13H21NO2Si MW: 251.40

O

73.1 135.1

236.2

0 50

100

Relative Int. (%)

100

150

200

I-5-N-ii

D O

50

250

120.2

73.1

300 MDA-d5, trimethylsilyl derivative

CD 3

CH–C– NHSi(CH3)3

C13H16D5NO2Si MW: 256.43

D

O

136.1

241.2

0 50

100

150

200

250

300


100 73.1

I-5-O-i

50

135.0

254.1

CH 3 O

CH 2 –CH– NSi(CH3)2C(CH3)3

O

COCF 3

MDA, trifluoroacetyl/ t-butyldimethylsilyl derivative C18H26F3NO3Si MW: 389.48

163.0

77.0 115.1

332.0

389.1

0 50

100

150

Relative Int. (%)

100

200 D

I-5-O-ii 73.1

O

136.0 115.1

300

350

400

MDA-d5, trifluoroacetyl/ t-butyldimethylsilyl derivative

258.1

CH–C– NSi(CH3)2C(CH3)3

C18H21D5F3NO3Si MW: 394.51

D COCF 3

O

50

250

CD 3

168.1 337.1

394.2

0 50

100

150

200

250 m/z



300

350

400

87


100

O

CH 3 CH 2 –CH– NSi(CH3)2C(CH3)3

O

COC 2 F 5

I-5-P-i

50 135.0

73.0

MDA, pentafluoropropionyl/ t-butyldimethylsilyl derivative

304.1

C19H26F5NO3Si MW: 439.49

163.0

382.0

439.1

0 50

100

150

200

Relative Int. (%)

100

D

I-5-P-ii

300

350

400

D COC 2 F 5

C19H21D5F5NO3Si MW: 444.52

73.0 136.0

115.1

450

MDA-d5, pentafluoropropionyl/ t-butyldimethylsilyl derivative

308.1

CH–C– NSi(CH3)2C(CH3)3

O

O

50

250

CD 3

168.1

387.1

444.2

0 50

100

Relative Int. (%)

100

150

200

250 m/z

CH 3

73.0 135.0 115.1

350

354.1

I-5-Q-i

50

300

O

CH 2 –CH– NSi(CH3)2C(CH3)3

O

COC 3 F 7

400

450

MDA, heptafluorobutyryl/ t-butyldimethylsilyl derivative C20H26F7NO3Si MW: 489.50

163.0

432.1 489.2

0 50

100

Relative Int. (%)

100

150

200

I-5-Q-ii

250 O

73.0 136.0 115.1

350

D CD 3 CH–C– NSi(CH3)2C(CH3)3

400 358.1

450

500

MDA-d5, heptafluorobutyryl/ t-butyldimethylsilyl derivative

D COC 3 F 7

O

50

300

C20H21D5F7NO3Si MW: 494.53

168.1 437.1 494.2

0 50

100

150

200

250

300 m/z



350

400

450

500

88

Figure I-6. Mass spectra of 3,4-methylenedioxymethamphetamine (MDMA) and its deuterated analog (MDMAd5): (A) underivatized; (B) acetyl-derivatized; (C) TCA-derivatized; (D) TFA-derivatized; (E) PFP-derivatized; (F) HFB-derivatized; (G) 4-CB-derivatized; (H) PFB-derivatized; (I) propylformyl-derivatized; (J,K) l-TPC-derivatized; (L,M) l-MTPA-derivatized; (N) TMS-derivatized. Relative Int. (%)

100

58.1

MDMA

CH 3

I-6-A-i

NH

C11H15NO2 MW: 193.24

CH 2 –CH–CH 3

O

50

O

77.0

135.0

0 50

100

Relative Int. (%)

100

62.1

150

200 MDMA-d5

CD 3

I-6-A-ii

D

50 78.0

NH

O

CH–C–CH 3

O

D

C11H10D5NO2 MW: 198.27

136.0

0 50

100

150

200


100

MDMA, acetyl derivative

58.1

162.1

I-6-B-i

CH 3

C13H17NO3 MW: 235.28

NCOCH3

50

CH 2 –CH–CH 3

O

100.1

O

135.1

77.1

235.2

0 50

100

Relative Int. (%)

100

150

200

250 MDMA-d5, acetyl derivative

62.1

I-6-B-ii 50

C13H12D5NO3 MW: 240.31

CD 3 D

104.1

164.1 136.1

78.1

NCOCH3

O

CH–C–CH 3

O

D

240.2

0 50

100

150 m/z

Relative Int. (%)

100

200

250

MDMA, trichloroacetyl derivative

162.1

I-6-C-i

202.0

CH 3

NCOCCl 3

50

135.1 56.1

77.1

92.1

CH 2 –CH–CH 3

O

116.9

O

337.1

0 50

100

150

200

Relative Int. (%)

100

50 96.1

300 CD 3

164.1

D

136.1 78.1

250

206.0

I-6-C-ii 59.1

C13H14Cl3NO3 MW: 338.61

117.0

350

MDMA-d5, trichloroacetyl derivative

NCOCCl 3

O

CH–C–CH 3

O

D

C13H9D5Cl3NO3 MW: 343.64 342.1

0 50

100

150

200 m/z



250

300

350

89


Relative Int. (%)

100

154.1

I-6-D-i

162.1

135.1

50

O

110.0

NCOCF3 CH 2 –CH–CH 3

C13H14F3NO3 MW: 289.25

O

77.1

69.1

MDMA, trifluoroacetyl derivative

CH 3

289.1

0 50

100

150

Relative Int. (%)

100

200

250

MDMA-d5, trifluoroacetyl derivative

158.1 CD 3

I-6-D-ii

136.1

D

164.1

50 113.1 78.1

69.1

300

NCOCF3

O

CH–C–CH 3

O

D

C13H9D5F3NO3 MW: 294.28 294.1

0 50

100

150

200

250

300


100

204.1

I-6-E-i 135.1

50

MDMA, pentafluoropropionyl derivative

CH 3

162.1 O

NCOC 2F 5 CH 2 –CH–CH 3

C14H14F5NO3 MW: 339.26

O

77.1

119.0

339.1

0 50

100

150

200

Relative Int. (%)

100

250

300

208.1

I-6-E-ii

D

136.1

50

NCOC 2F 5 CH–C–CH 3

O

C14H9D5F5NO3 MW: 344.29

D

O

119.0

78.1

MDMA-d5, pentafluoropropionyl derivative

CD 3

163.1

350

344.1

0 50

100

150

200 m/z

250

Relative Int. (%)

100

300

254.1

I-6-F-i 50

350

MDMA, heptafluorobutyryl derivative

162.1

CH 3

135.1

C15H14F7NO3 MW: 389.27

NCOC 3F 7

210.0

CH 2 –CH–CH 3

O

77.1

O

389.1

0 50

100

150

200

250

Relative Int. (%)

100

300

350

MDMA-d5, heptafluorobutyryl derivative CD

258.1

I-6-F-ii

D

50

136.1

164.1

213.1

400

3 NCOC 3F 7

O

CH–C–CH 3

O

D

C15H9D5F7NO3 MW: 394.30

78.1

394.2

0 50

100

150

200

250 m/z

Figure 1 — Stimulants


300

350

400

90


Relative Int. (%)

100

MDMA, 4-carboethoxyhexafluorobutyryl derivative

162.1

I-6-G-i 50 135.1

CH 2 –CH–CH 3

O O

280.1

262.1

195.0

105.1

CH 3 NCO(CF2)3COOC2H5

308.1

C18H19F6NO5 MW: 443.34

443.2


100

100

150

200

I-6-G-ii

164.1

250

300

350

MDMA-d5, 4-carboethoxyhexafluorobutyryl derivative

136.1

195.0

CD 3 D

284.1

266.1

78.1

NCO(CF2)3COOC2H5

O

CH–C–CH 3

O

D

448.2

0 50

100

150

200

250 m/z

Relative Int. (%)

100

300

350

400

CH 3

50

162.1

C18H14F5NO3 MW: 387.30

NCOC 6F 5

252.0

CH 2 –CH–CH 3

O O

135.1

77.1

387.0

0 50

100

150

200

Relative Int. (%)

100

250

300

195.0

350

D

50

256.0 164.1 136.1

3 NCOC 6F 5

O

CH–C–CH 3

O

D

C18H9D5F5NO3 MW: 392.33

392.0

0 100

400

MDMA-d5, 2,3,4,5,6-pentafluorobenzoyl derivative CD

I-6-H-ii 78.1

450

MDMA, 2,3,4,5,6-pentafluorobenzoyl derivative

195.0

I-6-H-i

50

450

312.2

C18H14D5F6NO5 MW: 448.37

50

400

150

200

250

300

350

400


100

144.1

I-6-I-i

CH 3

O

50

MDMA, propylformyl derivative

NCOOC3H7

58.1

102.0

C15H21NO4 MW: 279.33

CH 2 –CH–CH 3

O

135.0

77.0

162.0

279.1

220.1


100

100

150

200

148.1

I-6-I-ii 62.1

106.1 136.0

78.0

NCOOC3H7

O

CH–C–CH 3

O

D

165.1

300

MDMA-d5, propylformyl derivative

CD 3

D

50

250

C15H16D5NO4 MW: 284.36 284.2

225.1

0 50

100

150

200 m/z



250

300

91


Relative Int. (%)

100

166.0

I-6-J-i

N C

O

50

58.1

O

105.0

l-MDMA, (S)-(–)-N-(trifluoroacetyl)-prolyl derivative

H 3C O

162.1

N CH 2 CH O CCF 3 CH 3

135.0

C18H21F3N2O4 MW: 386.37

251.1

194.0

386.2

0

Relative Int. (%)

50

100

100

150

200

250

I-6-J-ii

D 3C D

50

62.1

O

163.1 136.0

O

CH CD CH 3

350

400

l-MDMA-d5, (S)-(–)-N-(trifluoroacetyl)-prolyl derivative

N C

O

96.0

300

166.0

C18H16D5F3N2O4 MW: 391.40

N O CCF 3

255.1

194.0

391.2

0 50

100

150

200

250

300

350

400


100

166.0

I-6-K-i

O

50

58.1

O

105.0

135.0

d-MDMA, (S)-(–)-N-(trifluoroacetyl)-prolyl derivative

H 3C O

162.1

N C N CH 2 CH O CCF 3 CH 3

C18H21F3N2O4 MW: 386.37

251.1

194.0

386.2

0 50

100

Relative Int. (%)

100

150

250

166.0

I-6-K-ii

50

200 D 3C D

164.1

62.1

O

96.0

O

CH CD CH 3

350

400

d-MDMA-d5, (S)-(–)-N-(trifluoroacetyl)-prolyl derivative

N C

O

136.0

300

C18H16D5F3N2O4 MW: 391.40

N O CCF 3

255.1

194.0

391.2

0 50

100

150

200

250

300

350

400


100

189.0

I-6-L-i

NCOC(CF3)(C6H5)OCH3

162.0

O

50

CH 2 –CH–CH 3

O

77.0

105.0

l-MDMA, (–)-α-methoxyα-trifluoromethylphenylacetyl derivative

CH 3

C21H22F3NO4 MW: 409.40

274.0

135.0

0 50

100

150

200

Relative Int. (%)

100

250

300

350

CD 3

I-6-L-ii

D

50 164.0 105.0

NCOC(CF3)(C6H5)OCH3

O

CH–C–CH 3

O

D

136.0

400

450

l-MDMA-d5, (–)-α-methoxyα-trifluoromethylphenylacetyl derivative

189.0

C21H17D5F3NO4 MW: 414.43 278.1

0 50

100

150

200

250 m/z



300

350

400

450

92


Relative Int. (%)

100

189.0

I-6-M-i 162.0

50

d-MDMA, (–)-α-methoxy-αtrifluoromethylphenylacetyl derivative

CH 3 NCOC(CF3)(C6H5)OCH3 CH 2 –CH–CH 3

O

C21H22F3NO4 MW: 409.40

O

77.0

105.0

274.1

135.0

0 50

100

150

200

Relative Int. (%)

100

250

189.0

I-6-M-ii

CD 3 D

50 164.0 105.0

300

NCOC(CF3)(C6H5)OCH3

O

CH–C–CH 3

O

D

350

400

450

d-MDMA-d5, (–)-α-methoxy-αtrifluoromethylphenylacetyl derivative C21H17D5F3NO4 MW: 414.43

278.1

136.0

0 50

100

150

Relative Int. (%)

100

200

250 m/z

350

400

CH 3 NSi(CH3)3

130.2

I-6-N-i 73.1

C14H23NO2Si MW: 265.43

O

58.1

450

MDMA, trimethylsilyl derivative

CH 2 –CH–CH 3

O

50

300

251.1

0 50

100

Relative Int. (%)

100

150

200

134.2

CD 3

I-6-N-ii

D

50 73.1

250

NSi(CH3)3

O

CH–C–CH 3

O

D

300

MDMA-d5, trimethylsilyl derivative C14H18D5NO2Si MW: 270.46 255.2

0 50

100

150

200 m/z



250

300

93

Figure I-7. Mass spectra of 3,4-methylenedioxyethylamphetamine (MDEA) and its deuterated analogs (MDEA-d5, -d6); (A) underivatized; (B) acetyl-derivatized; (C) TCA-derivatized; (D) TFA-derivatized; (E) PFP-derivatized; (F) HFBderivatized; (G) 4-CB-derivatized; (H) PFB-derivatized; (I) propylformyl-derivatized; (J,K) l-TPC-derivatized; (L,M) l-MTPA-derivatized; (N) TMS-derivatized. Relative Int. (%)

100

72.1

I-7-A-i

MDEA

CH 3 CH 2 –CH– NHCH2CH3

O

50

C12H17NO2 MW: 207.27

O

135.0

0 50

100

Relative Int. (%)

100

77.1

150

200

I-7-A-ii

250 MDEA-d5

CH 3 CH 2 –CH– NHCD2CD3

O

50

C12H12D5NO2 MW: 212.30

O

135.0

0 50

100

Relative Int. (%)

100

78.1

150

200

250 MDEA-d6

I-7-A-iii

CD 3

C12H11D6NO2 MW: 213.31

CH 2 –CH– NHCH2CD3

O

50

O

135.0

0 50

Relative Int. (%)

100

100

72.1

150 m/z

200

I-7-B-i 162.1

50 114.1

250

MDEA, acetyl derivative

CH 3 COCH 3

C14H19NO3 MW: 249.31

CH 2 –CH– NCH 2CH 3

O O

135.1


100

100 77.2

150

I-7-B-ii

200

250

MDEA-d5, acetyl derivative

162.1 CH 3 COCH 3

50

C14H14D5NO3 MW: 254.34

CH 2 –CH– NCD 2CD 3

O

119.1

300

O

135.1


100

100 78.2

150

I-7-B-iii

200 165.1

120.1

300 MDEA-d6, acetyl derivative

CD 3 COCH 3 CH 2 –CH– NCH 2CD 3

O

50

250

C14H13D6NO3 MW: 255.34

O

135.1

0 50

100

150

200 m/z



250

300

94


Relative Int. (%)

100

I-7-C-i

162.1

50

216.0

MDEA, trichloroacetyl derivative

135.1 56.1

77.1

O

106.1

351.1

0 50

100

150

200

Relative Int. (%)

100 162.1

I-7-C-ii 50

250

221.1

77.1

50 100

CH 3 COCCl 3 CH 2 –CH– NCD 2CD 3

O

150

200

250

300

222.1

I-7-C-iii

CD 3 COCCl 3 CH 2 –CH– NCH 2CD 3

O

135.1

400

C14H10D6Cl3NO3 MW: 358.68

O

112.1

357.1

0 100

350

MDEA-d6, trichloroacetyl derivative

165.1

50

50

C14H11D5Cl3NO3 MW: 357.67 356.1

100

59.1

400

O

111.1

77.1

350

MDEA-d5, trichloroacetyl derivative

135.1 58.1

300

0

Relative Int. (%)

C14H16Cl3NO3 MW: 352.64

CH 3 COCCl 3 CH 2 –CH– NCH 2CH 3

O

150

200

250

300

350

400


100

168.1

I-7-D-i

CH 3 COCF 3

162.1

50 135.1

O

140.1

MDEA, trifluoroacetyl derivative C14H16F3NO3 MW: 303.28


O

77.1

303.1


100

100

150

200

250

173.1

I-7-D-ii 135.1

O

141.1

CH 3 COCF 3 CH 2 –CH– NCD 2CD 3

C14H11D5F3NO3 MW: 308.31

O

77.1

350

MDEA-d5, trifluoroacetyl derivative

162.1

50

300

308.2


100

100

150

200

250

174.1

I-7-D-iii

165.1

50

CD 3 COCF 3 O

135.1

144.1

300

350

MDEA-d6, trifluoroacetyl derivative C14H10D6F3NO3 MW: 309.31

CH 2 –CH– NCH 2CD 3

O

309.2

77.1

0 50

100

150

200 m/z



250

300

350

95


Relative Int. (%)

100

MDEA, pentafluoropropionyl derivative

218.1

I-7-E-i

CH 3 COC 2 F 5 CH 2 –CH– NCH 2CH 3

162.1

50

O

190.0 135.1 77.1

C15H16F5NO3 MW: 353.28

O

119.0

353.1

0 50

100

150

200

Relative Int. (%)

100

250

300

CH 3 COC 2 F 5 CH 2 –CH– NCD 2CD 3

162.1

50

400

MDEA-d5, pentafluoropropionyl derivative

223.1

I-7-E-ii

O

191.0

C15H11D5F5NO3 MW: 358.31

O

135.1 77.1

350

119.0

358.1


100

100

150

200

250

300

350

224.1

I-7-E-iii

MDEA-d6, pentafluoropropionyl derivative

165.1

50

CD 3 COC 2 F 5 CH 2 –CH– NCH 2CD 3

O

135.1

194.1

400

C15H10D6F5NO3 MW: 359.32

O

119.0

77.1

359.2

0 50

100

150

200

250

300

350

400


100

268.1

I-7-F-i

MDEA, heptafluorobutyryl derivative

162.1

50

240.0 135.1

O


C16H16F7NO3 MW: 403.29

O

77.1

403.1

0 50

100

150

200

250

Relative Int. (%)

100

300

350

162.1

50

241.0 135.1

O

450

MDEA-d5, heptafluorobutyryl derivative

273.1

I-7-F-ii

400


C16H11D5F7NO3 MW: 408.32

O

77.1

408.2

0 50

100

150

200

250

Relative Int. (%)

100

300

350

274.1

I-7-F-iii 165.1

50

O

244.0

135.1

400

450

MDEA-d6, heptafluorobutyryl derivative CD 3 COC 3 F 7 CH 2 –CH– NCH 2CD 3

C16H10D6F7NO3 MW: 409.33

O

77.1

409.2

0 50

100

150

200

250 m/z



300

350

400

450

96


100

MDEA, 4-carboethoxyhexafluorobutyryl derivative C19H21F6NO5 MW: 457.36

50

162.1

I-7-G-i

322.2 O

135.1 195.0

105.1

276.1

CH 3 CO(CF2)3COOC2H 5 CH 2 –CH– NCH 2CH 3

O

294.1


100

100

150

MDEA-d5, 4-carboethoxyhexafluorobutyryl derivative

50

C19H16D5F6NO5 MW: 462.39

200

250

300

350

450

500

327.2

I-7-G-ii

162.1

400

O

CH 3 CO(CF2)3COOC2H 5 CH 2 –CH– NCD 2CD 3

O

135.1

281.1

195.0

105.1

299.1


100

100

150

C19H15D6F6NO5 MW: 463.40

250

165.1

MDEA-d6, 4-carboethoxyhexafluorobutyryl derivative

50

200

300

350

I-7-G-iii

400

450

500

328.2 O

CD 3 CO(CF2)3COOC2H 5 CH 2 –CH– NCH 2CD 3

O

135.1

223.1

195.0

300.1

281.1

0 50

100

150

200

250

300

350

400

450

500


100

195.0

MDEA, 2,3,4,5,6pentafluorobenzoyl derivative C19H16F5NO3 MW: 401.33

50

77.1

I-7-H-i 266.0

162.1

O


O

135.0


100

100

150

200 195.0

MDEA-d5, 2,3,4,5,6pentafluorobenzoyl derivative C19H11D5F5NO3 MW: 406.36

50

250

300

350

400

450

I-7-H-ii 271.0

162.1

O


O

77.1

135.0


100

100

150

200 195.0

MDEA-d6, 2,3,4,5,6pentafluorobenzoyl derivative

300

350

400

450

I-7-H-iii 272.1

C19H10D6F5NO3 MW: 407.36

50

250

165.1

O

CD 3 COC 6 F 5 CH 2 –CH– NCH 2CD 3

O

77.1

135.0

0 50

100

150

200

250 m/z



300

350

400

450

97


100

158.1

MDEA, propylformyl derivative

I-7-I-i 50

72.1

116.0

O

135.0

50

100

150

200


293.2

234.1

0

I-7-I-ii 77.1

50

250

163.1 CH 3 COOC 3H 7 CH 2 –CH– NCD 2CD 3

O

121.1

300

MDEA-d5, propylformyl derivative C16H18D5NO4 MW: 298.39

O

135.0

298.2

239.1

0 50

100


C16H23NO4 MW: 293.36

CH 3 COOC 3H 7 CH 2 –CH– NCH 2CH 3

O

150

200

300

MDEA-d6, propylformyl derivative

164.1

I-7-I-iii

CD 3 COOC 3H 7 CH 2 –CH– NCH 2CD 3

O

78.1

50

250

122.1

C16H17D6NO4 MW: 299.39

O

135.0

299.2

240.1

0 50

100

150

200

250

300


100

166.0

I-7-J-i 162.0

72.1

50 105.0

O

CH 3 O CH 2 CH N C

O

H 3CH 2C

135.0

l-MDEA, (S)-(–)-N-(trifluoroacetyl)-prolyl derivative

N

C19H23F3N2O4 MW: 400.39

O CCF 3

265.1

194.0

0 50

100

Relative Int. (%)

100

150

I-7-J-ii 77.1

200

250

166.0

CH 3 O

162.0

CH 2 CH

50

350

400

450

l-MDEA-d5, (S)-(–)-N-(trifluoroacetyl)-prolyl derivative

O

N C

D 3CD 2C

O

105.0

300

N

C19H18D5F3N2O4 MW: 405.42

O CCF 3

270.1

135.0 194.0

0 50

100

150

Relative Int. (%)

100

200

250

166.0

I-7-J-iii 78.1

50

108.1

136.0

0 50

100

150

300

O

CD 3 O CH 2 CH N C

O

D 3CH 2C

400

450

l-MDEA-d6, (S)-(–)-N-(trifluoroacetyl)-prolyl derivative N

C19H17D6F3N2O4 MW: 406.43

O CCF 3

271.1 194.0

200

250 m/z



350

300

350

400

450

98


100

166.0

I-7-K-i

O

CH 3 O CH 2 CH N C

O

H 3CH 2C

72.1

50

135.0

105.0

d-MDEA, (S)-(–)-N-(trifluoroacetyl)-prolyl derivative

N

C19H23F3N2O4 MW: 400.39

O CCF 3

265.1

194.0

0 50

100

150

Relative Int. (%)

100

200

250

350

CH 3

450

CH 2 CH N C

N

O

D 3CD 2C

O CCF 3

C19H18D5F3N2O4 MW: 405.42

270.1

135.0

105.0

O

O

77.1

400

d-MDEA-d5, (S)-(–)-N-(trifluoroacetyl)-prolyl derivative

166.0

I-7-K-ii 50

300

194.0

0 50

100

Relative Int. (%)

100

150

200

250

166.0

I-7-K-iii

CD 3 O

50

CH 2 CH

400

450

d-MDEA-d6, (S)-(–)-N-(trifluoroacetyl)-prolyl derivative N

C19H17D6F3N2O4 MW: 406.43

O CCF 3

271.1

194.0

135.0

350

O

N C

D 3CH 2C

O

78.1 108.1

300

0 50

RelativeInt. (%)

100

100

150

200

250 m/z

350

189.0

I-7-L-i

O

162.0 105.0


O

135.0

400

450

l-MDEA, (–)-α-methoxy-αtrifluoromethylphenylacetyl derivative

CH 3 COC(CF3)(C6H5)OCH3

50 77.0

300

C22H24F3NO4 MW: 423.43

288.1

214.0

0 50

100

150

200

Relative Int. (%)

100

250

300

350

189.0

I-7-L-ii

CH 3 COC(CF3)(C6H5)OCH3 O

50

162.0 77.0

105.0


O

135.0

400

450

l-MDEA-d5, (–)-α-methoxy-αtrifluoromethylphenylacetyl derivative C22H19D5F3NO4 MW: 428.46

293.1

219.1

0 50

100

150

200

Relative Int. (%)

100

250

O

50

165.0

350


105.0

135.0

450

C22H18D6F3NO4 MW: 429.46

O

294.1 77.0

400

l-MDEA-d6, (–)-α-methoxy-αCD 3 COC(CF3)(C6H5)OCH3 trifluoromethylphenylacetyl derivative

189.0

I-7-L-iii

300

217.0

0 50

100

150

200

250 m/z



300

350

400

450

99


Relative Int. (%)

100

189.0

I-7-M-i

d-MDEA, (–)-α-methoxy-αtrifluoromethylphenylacetyl derivative

CH 3 COC(CF3)(C6H5)OCH3 O

50

162.0


C22H24F3NO4 MW: 423.43

O

288.1 77.0

105.0

135.0

214.0

0 50

100

150

200

Relative Int. (%)

100

250

300

350

189.0

I-7-M-ii

CH 3 COC(CF3)(C6H5)OCH3

50

O

162.0 105.0

135.0

450

d-MDEA-d5, (–)-α-methoxy-αtrifluoromethylphenylacetyl derivative


O

77.1

400

C22H19D5F3NO4 MW: 428.46

293.1

219.1

0 50

100

150

200

Relative Int. (%)

100

250

50

O

165.1 105.0

400


O

77.0

350

450

d-MDEA-d6, (–)-α-methoxy-αtrifluoromethylphenylacetyl CD 3 COC(CF3)(C6H5)OCH3 derivative

189.0

I-7-M-iii

300

135.0

C22H18D6F3NO4 MW: 429.46

294.1

217.1

0 50

100

150

200

Relative Int. (%)

100

250 m/z

300

350

400

144.2

I-7-N-i 50

O

73.1

450

MDEA, trimethylsilyl derivative

CH 3 Si(CH3)3 CH 2 –CH– NCH 2CH 3

C15H25NO2Si MW: 279.45

O

135.1

264.2

0 50

100

150

Relative Int. (%)

100

200

149.2

I-7-N-ii

O

50 73.1

CH 3 Si(CH3)3 CH 2 –CH– NCD 2CD 3

250

300

MDEA-d5, trimethylsilyl derivative C15H20D5NO2Si MW: 284.48

O

135.1

269.2

0 50

100

150

Relative Int. (%)

100

200

150.2

I-7-N-iii 50

O

73.1

CD 3 Si(CH3)3 CH 2 –CH– NCH 2CD 3

250

300

MDEA-d6, trimethylsilyl derivative C15H19D6NO2Si MW: 285.49

O

135.1

270.2

0 50

100

150

200 m/z



250

300

100

Figure I-8. Mass spectra of N-methyl-1-(3,4-methylenedioxyphenyl)-2-butanamine (MBDB), and its deuterated analog (MBDB-d5): (A) underivatized; (B) acetyl-derivatized; (C) TCA-derivatized; (D) TFA-derivatized; (E) PFPderivatized; (F) HFB-derivatized; (G) 4-CB-derivatized; (H) PFB-derivatized; (I) propylformyl-derivatized; (J,K) lTPC-derivatized; (L,M) l-MTPA-derivatized; (N) TMS-derivatized. Relative Int. (%)

100

72.1

I-8-A-i

O

C12H17NO2 MW: 207.27

CH 2CH 3

O

50 135.0

88.6

178.1

0 50

100

100 Relative Int.(%)

MBDB

CH 2 –CH– NHCH3

76.1

150

200

I-8-A-ii

D O

50 136.0

MBDB-d5

D

CH–C– NHCD3

C12H12D5NO2 MW: 212.30

CH 2CH 3

O

91.1

250

182.1

0 50

Relative Int. (%)

100

100

72.1

150 m/z

200

MBDB, acetyl derivative

I-8-B-i

C14H19NO3 MW: 249.31

COCH 3

176.1

50

250

O

114.1

CH 2 –CH– NCH3 CH 2CH 3

O

135.1


100

100 76.2

150

200

250

300

MBDB-d5, acetyl derivative

I-8-B-ii

C14H14D5NO3 MW: 254.34

D COCH 3 CH–C– NCD3 D

50

O

118.1

178.1

CH 2CH 3

O

136.1

0 50

100

150

200

250

300


100

I-8-C-i

176.1 216.0 COCCl 3

135.1

O

50

CH 2CH 3

351.1

0 50

100

100 relative Int. (%)

C14H16Cl3NO3 MW: 352.64

CH 2 –CH– NCH3

O

117.0

77.1

MBDB, trichloroacetyl derivative

150

200

I-8-C-ii

250

300

220.1 D

177.1 O

136.1

50

O

78.1

D COCCl 3 CH–C– NCD3 CH 2CH 3

117.0

100

150

200

250 m/z



400

MBDB-d5, trichloroacetyl derivative C14H11D5Cl3NO3 MW: 357.67 356.1

0 50

350

300

350

400

101


Relative Int. (%)

100

MBDB, trifluoroacetyl derivative

168.1

C14H16F3NO3 MW: 303.28

50

I-8-D-i

176.1

COCF 3 CH 2 –CH– NCH3

O

135.1

CH 2CH 3

O

110.1

77.1

303.1


100

100

150

MBDB-d5, trifluoroacetyl derivative

250

300

I-8-D-ii D COCF 3 CH–C– NCD3 D

O

178.1

136.1

CH 2CH 3

O

113.1

78.1

350

172.1

C14H11D5F3NO3 MW: 308.31

50

200

308.2

0 50

Relative Int. (%)

100

100

150

200 m/z

MBDB, pentafluoropropionyl derivative C15H16F5NO3 MW: 353.28

50

250

350

218.1 O

COC 2 F 5 CH 2 –CH– NCH3

O

CH 2CH 3

176.1 135.1 160.0

77.1

300

I-8-E-i

119.0

353.1


100

100

150

200

MBDB-d5, pentafluoropropionyl derivative C15H11D5F5NO3 MW: 358.31

50

78.1

250

300

350

222.1

400

I-8-E-ii D COC 2 F 5 CH–C– NCD3 D

O

178.1

136.1

163.1

CH 2CH 3

O

358.2

119.0

0 50

100

150

200

250

300

350

400


100

268.1

MBDB, heptafluorobutyryl derivative C16H16F7NO3 MW: 403.29

50

O

135.1

I-8-F-i

COC 3 F 7

176.1 210.0


O

77.1

403.1


100

100

150

200

250

C16H11D5F7NO3 MW: 408.32

350

400

272.1

MBDB-d5, heptafluorobutyryl derivative

50

300

I-8-F-ii

D COC 3 F 7 CH–C– NCD3 D

O

136.1

178.1

O

213.1

450

CH 2CH 3

78.1

408.2

0 50

100

150

200

250 m/z



300

350

400

450

102


Relative Int. (%)

100

MBDB, 4-carboethoxyhexafluorobutyryl derivative

176.1

I-8-G-i

322.2

C19H21F6NO5 MW: 457.36

50

CO(CF2)3COOC2H 5 CH 2 –CH– NCH3

O

135.1

276.1

CH 2CH 3

O

294.1

77.1


100

100

150

200

250

300

MBDB-d5, 4-carboethoxyhexafluorobutyryl derivative C19H16D5F6NO5 MW: 462.39

50

350

400

450

D

D CO(CF2)3COOC2H 5

326.2

I-8-G-ii 178.1

136.1

280.1

78.1

500

298.1

O

CH–C– NCD3

O

CH 2CH 3

224.1

0 50

100

150

200

250

300

350

400

450

500


100

MBDB, 2,3,4,5,6-pentafluorobenzoyl derivative

195.0

C19H16F5NO3 MW: 401.33

50

I-8-H-i O

COC 6 F 5 CH 2 –CH– NCH3

O

CH 2CH 3

266.0

176.1 135.0

77.1


100

100

150

200

250

195.0

MBDB-d5, 2,3,4,5,6-pentafluorobenzoyl derivative

350

I-8-H-ii

C19H11D5F5NO3 MW: 406.36

50

300

450

D D COC 6 F 5 CH–C– NCD3

O

270.1

400

CH 2CH 3

O

178.1 136.1

78.1

0 50

100

150

200

Relative Int. (%)

100

250 m/z

158.1

300

350

400

MBDB, propylformyl derivative

I-8-I-i COOC 3H 7

50

116.1

72.1

O

135.0

C16H23NO4 MW: 293.36


O

234.1

293.2

0 50

100

150

relative Int. (%)

100

162.1

50

200

D

136.0

250

300

MBDB-d5, propylformyl derivative

I-8-I-ii

120.1

76.1

450

C16H18D5NO4 MW: 298.39

D COOC 3H 7

O

CH–C– NCD3

O

CH 2CH 3

239.1

298.2

0 50

100

150

200 m/z



250

300

103


100

166.0

I-8-J-i

l-MBDB, (S)-(–)-N-(trifluoroacetyl)-prolyl derivative

H 3C O

176.1

72.1

O

50

CH 2 CH

N C N CH 2CH 3 O CCF 3

O

135.0 96.0

C19H23F3N2O4 MW: 400.39

265.1

194.0

400.2

0 50

100

Relative Int. (%)

100

150

200

250

300

166.0

I-8-J-ii

H

76.1

CD

O

50

O

178.1 136.0

D 3C O

350

400

l-MBDB-d5, (S)-(–)-N-(trifluoroacetyl)-prolyl derivative

CD N C N CH 2CH 3 O CCF 3

C19H18D5F3N2O4 MW: 405.42

269.1

96.0

450

405.2

194.0

0 50

100

Relative Int. (%)

100

150

200

166.0

I-8-K-i

250 m/z

350

176.1 O

CH 2 CH N C

135.0 96.0

265.1

194.0

400.2

0 50

100

Relative Int. (%)

100

150

I-8-K-ii

200

300 H

CD

O

76.1

50

250

166.0 178.1

O

D 3C O

CD

450

C19H23F3N2O4 MW: 400.39

N CH 2CH 3 O CCF 3

O

400

d-MBDB, (S)-(–)-N-(trifluoroacetyl)-prolyl derivative

H 3C O

72.1

50

300

N C

350

400

450

d-MBDB-d5, (S)-(–)-N-(trifluoroacetyl)-prolyl derivative

N CH 2CH 3 O CCF 3

C19H18D5F3N2O4 MW: 405.42

136.0 269.1

194.0

96.0

405.2

0 50

100

150

200

Relative Int. (%)

100

250 m/z

300

350

189.0

I-8-L-i O

176.0


O

77.0

105.0

C22H24F3NO4 MW: 423.43

288.1

135.0

450

l-MBDB, (–)-α-methoxy-αtrifluoromethylphenylacetyl derivative

COC(CF3)(C6H5)OCH3

50

400

0 50

100

150

200

relative Int. (%)

100

250

300

189.0

I-8-L-ii

D

O

50

178.1 105.0

O

D COC(CF3)(C6H5)OCH3 CH–C– NCD3

350

450

l-MBDB-d5, (–)-α-methoxy-αtrifluoromethylphenylacetyl derivative C22H19D5F3NO4 MW: 428.46

CH 2CH 3

292.1

136.0

400

0 50

100

150

200

250 m/z



300

350

400

450

104


100

189.0

I-8-M-i

d-MBDB, (–)-α-methoxy-αtrifluoromethylphenylacetyl derivative

COC(CF3)(C6H5)OCH3

176.1

CH 2 –CH– NCH3

O

50

CH 2CH 3

O

135.0

C22H24F3NO4 MW: 423.43

288.1

105.0

77.0


100

100

150

200

I-8-M-ii

D

50 105.0

78.0

250

300

189.0

178.1 136.0

D COC(CF3)(C6H5)OCH3

O

CH–C– NCD3

O

CH 2CH 3

350

400

450

d-MBDB-d5, (–)-α-methoxy-αtrifluoromethylphenylacetyl derivative C22H19D5F3NO4 MW: 428.46

292.1

0 50

100

150

200

Relative Int. (%)

100

250 m/z

300

350

400

MBDB, trimethylsilyl derivative

144.2

I-8-N-i

Si(CH3)3

50

CH 2CH 3

O

73.1

C15H25NO2Si MW: 279.45

CH 2 –CH– NCH3

O

450

135.1

264.2

0 50

100

150

Relative Int. (%)

100

200

148.2

I-8-N-ii

D

50 73.1

D Si(CH3)3

O

CH–C– NCD3

O

CH 2CH 3

250

300

MBDB-d5, trimethylsilyl derivative C15H20D5NO2Si MW: 284.48 269.2

136.1

0 50

100

150

200 m/z



250

300

105

Figure I-9. Mass spectra of selegiline and its deuterated analog (selegiline-d8).

Relative Int. (%)

100

96.1

Selegiline (CAS NO.14611-51-9)

I-9-i CH 3

50

CH 2 –CH– N

56.1

CH 2 C CH 3

CH

C13H17N MW: 187.28

91.0

0 50

100

Relative Int. (%)

100

150

200

103.1

Selegiline-d8

I-9-ii D

62.1

CD 3

CH 2 C CH–C– N CD 3 D

50

CH

C13H9D8N MW: 195.33

92.0

0 50

100

150 m/z



200

106

Figure I-10. Mass spectra of N-desmethylselegiline and its deuterated analogs (N-desmethylselegiline-d11): (A) underivatized; (B) acetyl-derivatized; (C) TCA-derivatized; (D) TFA-derivatized; (E) PFP-derivatized; (F) HFBderivatized; (G) 4-CB-derivatized; (H) TMS-derivatized. Relative Int. (%)

100

82.1

I-10-A-i

N-Desmethylseleginine (CAS NO.18913-84-3) C12H15N MW: 173.25

CH 3 CH 2 –CH– NH– CH 2 C CH

50 91.0

65.0

0 50

100

Relative Int. (%)

100

150

200

86.1

I-10-A-ii

N-Desmethylseleginine-d11 D

D D

50

CD 3

C12H4D11N MW: 184.32

CD 2 –C– NH– CH 2 C CH

D

D

D

98.1

70.1

0 50

100

150

200


100

82.1

I-10-B-i

N-Desmethylseleginine, acetyl derivative

CH 3 COCH 3

91.0

65.1

215.1


C14H17NO MW: 215.29

CH 2 –CH– N– CH 2 C CH

124.1

50

100

150

200

86.1

I-10-B-ii

128.1

50

D

D

D

D

D

250 N-Desmethylseleginine-d11, acetyl derivative

CD 3 CD 2 –C– N– CH 2 C CH

C14H6D11NO MW: 226.36

D COCH 3

98.1

70.1

226.2

0 50

Relative Int. (%)

100

100

150 m/z

CH 3 CH 2 –CH– N– CH 2 C CH

91.0

250

N-Desmethylseleginine, trichloroacetyl derivative

225.9

I-10-C-i

50

200

C14H14Cl3NO MW: 318.63

COCCl 3

118.0 65.0

318.9

0 50

100

150

200

Relative Int. (%)

100

229.9

I-10-C-ii

D

D

D

D

D

98.1

50

250

128.1

300

N-Desmethylseleginine-d11, trichloroacetyl derivative

CD 3

C14H3D11Cl3NO MW: 329.69

CD 2 –C– N– CH 2 C CH D COCCl 3

70.0

329.0

0 50

100

150

200 m/z



350

250

300

350

107


Relative Int. (%)

100

178.0

N-Desmethylseleginine, trifluoroacetyl derivative

I-10-D-i CH 3

50

118.1 91.1

55.1

C14H14F3NO MW: 269.26

CH 2 –CH– N– CH 2 C CH COCF 3

0 50

100

150

200

Relative Int. (%)

100

250

182.1

I-10-D-ii

D

D

D

50

128.1

D

98.1

D

300

N-Desmethylseleginine-d11, trifluoroacetyl derivative CD 3 CD 2 –C– N– CH 2 C CH

C14H3D11F3NO MW: 280.33

D COCF 3

59.1

0 50

100

150

200

250

300


100

50

N-Desmethylseleginine, pentafluoropropionyl derivative

228.0

I-10-E-i


118.1

C15H14F5NO MW: 319.27

COC 2 F 5

91.0 55.1

0 50

100

150

200

Relative Int .(%)

100

250

300

232.0

I-10-E-ii

D

50

D

D

128.1

98.1

D

59.1

D

350

400

N-Desmethylseleginine-d11, pentafluoropropionyl derivative

CD 3 CD 2 –C– N– CH 2 C CH D COC 2 F 5

C15H3D11F5NO MW: 330.34

0 50

100

150

200

250

300

350

400


100

278.0

I-10-F-i


50 91.1

N-Desmethylseleginine, heptafluorobutyryl derivative C16H14F7NO MW: 369.28

COC 3 F 7

118.1

55.1

169.0

0 50

100

150

200

250

Relative Int. (%)

100

300 282.0

I-10-F-ii

D

D

D

D

D

50

98.1

128.1

59.1

CD 3 CD 2 –C– N– CH 2 C CH

350

400

N-Desmethylseleginine-d11, heptafluorobutyryl derivative C16H3D11F7NO MW: 380.34

D COC 3 F 7

169.0

0 50

100

150

200

250 m/z



300

350

400

108


Relative Int. (%)

100

332.0

I-10-G-i

CH 2 –CH– N– CH 2 C CH

91.1 118.1

50

N-Desmethylseleginine, 4-carboethoxyhexafluorobutyryl derivative

CH 3

C19H19F6NO3 MW: 423.35

CO(CF2)3COOC2H 5

195.0

65.1

304.0

423.1


100

100

150

200

250

300

350

400

336.0

I-10-G-ii

D

D

CD 2 –C– N– CH 2 C CH

D

128.1

C19H8D11F6NO3 MW: 434.42

D CO(CF2)3COOC2H 5

D

194.9

70.1

N-Desmethylseleginine-d11, 4-carboethoxyhexafluorobutyryl derivative

CD 3

D

98.1

50

450

434.1

308.0

0 50

100

150

200

Relative Int. (%)

100

250 m/z

300

400

154.1

I-10-H-i

450

N-Desmethylseleginine, trimethylsilyl derivative


73.1

50

350

C15H23NSi MW: 245.44

Si(CH3)3

91.1

230.1

0 50

100

150

Relative Int. (%)

100

200 158.1

I-10-H-ii

D

D

D

50

73.1

D

CD 3

250

N-Desmethylseleginine-d11, trimethylsilyl derivative C15H12D11NSi MW: 256.50

CD 2 –C– N– CH 2 C CH D Si(CH3)3

D

98.1

300

241.2

0 50

100

150

200 m/z



250

300

109

Figure I-11. Mass spectra of fenfluramine and its deuterated analogs (fenfluramine-d10): (A) underivatized; (B) acetylderivatized; (C) TCA-derivatized; (D) TFA-derivatized; (E) PFP-derivatized; (F) HFB-derivatized; (G) 4-CB-derivatized. Relative Int. (%)

100

72.1

CH 3 CH 2–CH–NH–CH 2CH 3

50

CF 3

Fenfluramine (CAS NO.458-24-2)

I-11-A-i

C12H16F3N MW: 231.26

159.0

109.1

212.1

231.1

0 50

100

Relative Int. (%)

100

150

81.1

200

CD 3 CH–C–NH–CD 2CD 3 D

50

250 Fenfluramine-d10

I-11-A-ii

C12H6D10F3N MW: 241.32

D

CF 3

160.0

110.1

223.1

240.2

0 50

100

Relative Int. (%)

100

150 m/z

200

72.0 114.0

CH 2 –CH–N–CH 2 CH 3

50

50

100

C14H18F3NO MW: 273.29

COCH 3

CF 3

159.0

87.0

100

Fenfluramine, acetyl derivative

I-11-B-i

CH 3

216.0

0

Relative Int. (%)

250

150

200

254.1

250

300

81.1

I-11-B-ii

CD 3

123.1

CH–C–N–CD 2 CD 3

50

D

160.0

223.0

0 50

100

C14H8D10F3NO MW: 283.35

D COCH 3

CF 3

87.0

150

Fenfluramine-d10, acetyl derivative

200

264.1

250

300


100

216.0

I-11-C-i

CH 3 CH 2 –CH–N–CH 2 CH 3

159.0

50 70.0

COCCl 3

CF 3

187.0

Fenfluramine, trichloroacetyl derivative C14H15Cl3F3NO MW: 376.63

361.9

0 50

100

Relative Int. (%)

100

150

200

250

300

225.0

I-11-C-ii

CH–C–N–CD 2 CD 3 D

161.0 62.1

CF 3

D COCCl 3

C14H5D10Cl3F3NO MW: 386.69

192.0

74.0

370.1

0 50

100

150

200

250 m/z



400

Fenfluramine-d10, trichloroacetyl derivative

CD 3

50

350

300

350

400

110


Relative Int. (%)

100

168.0

CH 3

Fenfluramine, trifluoroacetyl derivative

I-11-D-i

CH 2 –CH–N–CH 2 CH 3

50

COCF 3

CF 3

C14H15F6NO MW: 327.27

140.0 159.0

70.1

186.1

308.1

0 50

100

150

200

Relative Int. (%)

100

177.1

300

I-11-D-ii

CD 3 D CF 3

D COCF 3

145.0 74.1

50

100

C14H5D10F6NO MW: 337.33 160.0

318.1

192.1

150

200 m/z

100

250

218.0

300

I-11-E-i

CH 3 CH 2 –CH–N–CH 2 CH 3

50

350 Fenfluramine-d10, trifluoroacetyl derivative


50

0

Relative Int. (%)

250

350

Fenfluramine, pentafluoropropionyl derivative C15H15F8NO MW: 377.27

COC 2 F 5

CF 3

190.0

75.0

159.0

119.0

358.0

0 50

100

150

200

250

Relative Int. (%)

100

300

227.1

350

I-11-E-ii

CD 3 CH–C–N–CD 2 CD 3

50

D CF 3

0 50

195.0

100

Fenfluramine-d10, pentafluoropropionyl derivative C15H5D10F8NO MW: 387.33

D COC 2 F 5

160.0

119.0

74.1

400

150

368.1

200

250

300

350

400


100

268.0 CH 2 –CH–N–CH 2 CH 3

50

240.0 159.0

70.1

50

Fenfluramine, heptafluorobutyryl derivative C16H15F10NO MW: 427.28

COC 3 F 7

CF 3

0

100

150

408.0

200

250


I-11-F-i

CH 3

300 277.1

CD 3

350

I-11-F-ii


50

D CF 3

400

Fenfluramine-d10, heptafluorobutyryl derivative C16H5D10F10NO MW: 437.34

D COC 3 F 7

245.0 160.0

62.1

418.1

0 50

100

150

200

250 m/z



450

300

350

400

450

111


Relative Int. (%)

100

322.0 CH 2 –CH–N–CH 2 CH 3

50

159.0 70.1

Fenfluramine, 4-carboethoxyhexafluorobutyryl derivative

CH 3

I-11-G-i

186.0

109.0

C19H20F9NO3 MW: 481.35

CO(CF2)3COOC2H 5

CF 3

220.0

276.0

294.0

462.1

0 50

100

150

200

250

300

350

Relative Int. (%)

100

I-11-G-ii

331.1

CD 3 D

161.0

CF 3

195.0

119.0

D CO(CF2)3COOC2H 5

224.0

284.0

450

C19H10D10F9NO3 MW: 491.41 303.0

472.2

0 50

100

150

200

250

300 m/z



500

Fenfluramine-d10, 4-carboethoxyhexafluorobutyryl derivative


50 62.1

400

350

400

450

500

112

Figure I-12. Mass spectra of norcocaine, and its deuterated analog (norcocaine-d3): (A) underivatized; (B) TFAderivatized; (C) PFP-derivatized; (D) HFB-derivatized; (E) TMS-derivatized. Relative Int. (%)

100

168.1

Norcocaine

I-12-A-i

H

COOCH3 O H

N

50

68.0 77.0

105.0

O

136.0

108.0

C16H19NO4 MW: 289.33

C

H

289.1

0 50

100

150

200

Relative Int. (%)

100

I-12-A-ii 68.1

H

COOCD3 O H O C H

136.0

77.0

105.0

300 Norcocaine-d3

N

50

250

171.1

108.1

C16H16D3NO4 MW: 292.34

292.1

0 50

100

150

200

250

300

m/z Relative int. (%)

100

105.1

I-12-B-i

F 3COC

N

O

50

164.1

77.1

Norcocaine, trifluoroacetyl derivative

COOCH3 O H

C

194.1

C18H18F3NO5 MW: 385.33

263.1

H

232.1

280.1

316.1

385.2

0 50

100

Relative int. (%)

100

150 105.1

200

I-12-B-ii

F 3COC N

50

164.1

77.1

197.1

250

300

350

Norcocaine-d3, trifluoroacetyl derivative

COOCD3 O H O C H

C18H15D3F3NO5 MW: 388.35

266.1

232.1

283.1

319.2

0 50

100

150

200

400

250

300

388.1

350

400


100

105.1

I-12-C-i

F 5 C 2 OC N

50

O

214.1 77.1

C

226.1

166.1

330.1

0 50

100

Relative Int. (%)

100

150

200

105.1

50

250 F 5 C 2 OC

I-12-C-ii

300

N

O

C

400

333.1

438.2

0 50

100

150

200

250 m/z



450

C19H15D3F5NO5 MW: 438.36

316.1

226.1

169.1

435.2

Norcocaine-d3, pentafluoropropionyl derivative

H

197.1 119.1

350

COOCD3 O H

214.1 77.1

C19H18F5NO5 MW: 435.34

313.1

H

194.1 119.1

Norcocaine, pentafluoropropionyl derivative

COOCH3 O H

300

350

400

450

113


100

105.0

F 7 C 3 OC

O

50

C

264.0

H

77.0

Norcocaine, heptafluorobutyryl derivative

I-12-D-i

COOCH3 O H

N

194.0 333.9

119.0

100

Relative Int. (%)

100

150 105.0

200

F 7 C 3 OC

250

COOCD3 O H

N

O

50

300

350

400

264.0

C20H15D3F7NO5 MW: 488.37

366.0

197.0 337.0

383.1

0 100

150

200

250

300

500

Norcocaine-d3, heptafluorobutyryl derivative

I-12-D-ii

119.0

50

450

C

H

77.0

485.1

380.0

0 50

C20H18F7NO5 MW: 485.35

363.0

350

488.1

400

450

500


100

I-12-E-i 73.0

(CH3)3Si

140.0

N

50 152.0

Norcocaine, trimethylsilyl derivative

240.1

179.0

105.0

224.0

COOCH3 O H O C H

C19H27NO4Si MW: 361.51 361.1

346.1

256.1


100

100

150

200

I-12-E-ii 105.0

73.0

250 243.1

140.0

179.0

300

(CH3)3Si

N

350

COOCD3 O H

O

50

C

349.1

H

152.0

400 Norcocaine-d3, trimethylsilyl derivative

C19H24D3NO4Si MW: 364.53 364.1

259.1

224.1

0 50

100

150

200

250 m/z



300

350

400

114

Figure I-13. Mass spectra of cocaine, and its deuterated analog (cocaine-d3).

Relative Int. (%)

100

I-13-i

82.0

182.1 N

50

105.0

77.0

Cocaine (CAS NO.50-36-2)

CH 3 COOCH 3 O H O C H

C17H21NO4 MW: 303.35

303.1 272.1

198.1

122.1

0 50

100

Relative Int. (%)

100

150

I-13-ii

85.1

200

250

185.1 CD 3 COOCH 3 N O H O

50 77.0

300

Cocaine-d3 (CAS NO.65266-73-1) C17H18D3NO4 MW: 306.37

C

H

105.0

306.1 275.1

201.1

125.1

350

0 50

100

150

200 m/z



250

300

350

115

Figure I-14. Mass spectra of cocaethylene, and its deuterated analog (cocaethylene-d3,-d8). Relative Int. (%)

100

I-14-i

82.0

196.1

Cocaethylene (CAS NO.529-38-4) CH 3 COOCH CH 2 3 N O H

50

O

105.0

77.0

C

H

122.1

317.1

272.1

212.1

166.0

C18H23NO4 MW: 317.38

0 50

100

Relative Int. (%)

100

150

85.1

200

250

199.1

I-14-ii

O

105.0

320.1

275.1

215.1

169.1

C18H20D3NO4 MW: 320.40

C

H

125.1

350

Cocaethylene-d3 (CAS NO.136765-30-5) CD 3 COOCH CH 2 3 N O H

50 77.0

300

0 50

100

Relative Int. (%)

100

150

200

85.1

250

N

50

H

125.1

220.1

169.1

C18H15D8NO4 MW: 325.43

CD 3 COOCD CD 2 3 O H O

105.0

77.0

350

Cocaethylene-d8 (CAS NO.152521-09-0)

204.1

I-14-iii

300

C

325.2

275.1

0 50

100

150

200 m/z



250

300

350

116

Figure I-15. Mass spectra of ecgonine methyl ester, and its deuterated analog (ecgonine methyl ester-d3): (A) underivatized; (B) TFA-derivatized; (C) PFP-derivatized; (D) HFB-derivatized; (E) TMS-derivatized; (F) t-BDMSderivatized. Relative Int. (%)

100

82.1 96.1

N

I-15-A-i

CH 3 COOCH 3 H

Ecgonine methyl ester (CAS NO.7143-09-1) C10H17NO3 MW: 199.24

OH

50

H

55.1

112.0

168.1

140.1

199.1

182.1

0 50

100

Relative Int. (%)

100

150

85.1 N

99.1

200

CD 3 COOCH 3 H

250

I-15-A-ii

Ecgonine methyl ester-d3 (CAS NO.136765-34-9) C10H14D3NO3 MW: 202.26

OH

50

H

115.1

60.1

171.1

143.1

202.1

185.1

0 50

100

150 m/z

Relative Int. (%)

100

200

182.1 CH 3 COOCH 3 N H

82.0

50

94.0

H

I-15-B-i

Ecgonine methyl ester, trifluoroacetyl derivative C12H16F3NO4 MW: 295.25

OOC–CF 3

295.1

69.0 122.1

250

264.0

154.1

0 50

100

150

Relative Int. (%)

100

200

250

185.1 85.0

50

N

I-15-B-ii

CD 3 COOCH 3 H

97.0

H

300

C12H13D3F3NO4 MW: 298.27

OOC–CF 3

69.0 125.1

350

Ecgonine methyl ester-d3, trifluoroacetyl derivative

298.1

267.1

157.1

0 50

100

150

Relative Int. (%)

100

200 m/z 182.1

250

CH 3 COOCH 3 N H

82.0

50

H

94.0

300

I-15-C-i

Ecgonine methyl ester, pentafluoropropionyl derivative

OOC–C 2 F 5

C13H16F5NO4 MW: 345.26

119.0

69.0

350

345.0 314.0

0 50

100

150

Relative Int. (%)

100

200

250

185.1 N

CD 3 COOCH 3 H

85.0

50

H

97.0

I-15-C-ii

350

400

Ecgonine methyl ester-d3, pentafluoropropionyl derivative

OOC–C 2 F 5

118.9

69.0

300

C13H13D3F5NO4 MW: 348.28 317.0

348.1

0 50

100

150

200

250 m/z



300

350

400

117


Relative Int. (%)

100

182.1 82.0

50 69.0

H

94.0 119.0

Ecgonine methyl ester, heptafluorobutyryl derivative

I-15-D-i

CH 3 COOCH 3 N H

C14H16F7NO4 MW: 395.27

OOC–C 3 F 7

395.1

364.0

168.9

0 50

100

150

200

Relative Int. (%)

100

250

300

350

400

185.1 CD 3 COOCH 3 N H

85.0

50 69.0

H

97.1 119.0

I-15-D-ii

450

Ecgonine methyl ester-d3, heptafluorobutyryl derivative C14H13D3F7NO4 MW: 398.29

OOC–C 3 F 7

398.1

367.0

169.0

0 50

100

Relative Int. (%)

100

150

200

250 m/z

82.0 N

96.1

300

CH 3 COOCH 3 H

H

50 73.0

350

450

Ecgonine methyl ester, trimethylsilyl derivative

I-15-E-i

OSi(CH3)3

C13H25NO3Si MW: 271.43

182.1

155.0

400

271.1

240.1

0 50

100

Relative Int. (%)

100

150

200

85.1 99.1

N

CD 3 COOCH 3 H

50

H

73.0

250

I-15-E-ii

Ecgonine methyl ester-d3, trimethylsilyl derivative C13H22D3NO3Si MW: 274.45

OSi(CH3)3

185.1

158.1

300

243.1

274.1

0 50

100

150

200

250

300


100

82.1 N

50

CH 3 COOCH 3 H

96.1

H

I-15-F-i

OSi(CH3)2C(CH3)3

182.1

C16H31NO3Si MW: 313.51

256.1

155.0

73.0

Ecgonine methyl ester, t-butyldimethylsilyl derivative

282.1

313.1

0 50

100

Relative Int. (%)

100

150

200

85.1 N

50

250

CD 3 COOCH 3 H

99.1

H

I-15-F-ii

C16H28D3NO3Si MW: 316.53

259.1

158.1

350

Ecgonine methyl ester-d3, t-butyldimethylsilyl derivative

OSi(CH3)2C(CH3)3

185.1 73.0

300

285.1

316.1

0 50

100

150

200 m/z



250

300

350

118

Figure I-16. Mass spectra of benzoylecgonine and its deuterated analog (benzoylecgonine-d3,-d8): (A) methylderivatized; (B) ethyl-derivatized; (C) propyl-derivatized; (D) butyl-derivatized; (E) PFPoxy-derivatized; (F) HFPoxyderivatized; (G) TMS-derivatized; (H) t-BDMS-derivatized.

Relative Int. (%)

100

82.0

I-16-A-i

182.1 N

CH 3

H O H

50 105.0

77.0

COOCH3

Benzoylecgonine (CAS NO.519-09-5) methyl derivative C17H21NO4 MW: 303.35

O C

303.1

198.1

122.0

272.0

0 50

100

Relative Int. (%)

100

150

85.0

I-16-A-ii

200

250

N

CD 3

105.0 123.0

COOCH3 H O H

350

Benzoylecgonine-d3, methyl derivative

185.1

50 77.0

300

O

C17H18D3NO4 MW: 306.37

C

306.1 275.1

201.1

0 50

100

Relative Int. (%)

100

150

I-16-A-iii

85.0

200

250

N

CD 3

50 82.0

300

185.1

110.0

COOCH3 OD H O C H D

Benzoylecgonine-d8, methyl derivative

D

C17H13D8NO4 MW: 311.40 311.1

D D

280.1

201.1

125.1

350

0 50

100

150

Relative Int. (%)

100

I-16-B-i

82.0

200 m/z

250

196.1 N

CH 3

C18H23NO4 MW: 317.38

C

H

105.0 122.0

317.1

272.1

212.1

166.0

350

Benzoylecgonine, ethyl derivative

COOC 2H 5 O H O

50 77.0

300

0 50

100

Relative Int. (%)

100

150

85.1

I-16-B-ii

200

250

199.1 N

CD 3

C18H20D3NO4 MW: 320.40 320.1

C

H

105.0 125.1

275.1

215.1

169.1

350

Benzoylecgonine-d3, ethyl derivative

COOC 2H 5 O H

O

50 77.0

300

0 50

100

Relative Int. (%)

100

85.1

150

I-16-B-iii

200

250 CD 3

COOC 2H 5 OD H

O

50 110.0 125.1

D

C18H15D8NO4 MW: 325.43 325.1

D

C

H

D

350

Benzoylecgonine-d8, ethyl derivative

199.1 N

82.1

300

D

280.1

215.1

169.1

0 50

100

150

200 m/z



250

300

350

119


Relative Int. (%)

100 82.1 N

105.1 77.1

Benzoylecgonine, propyl derivative

I-16-C-i

O

H O H

50

210.2

COOC 3H 7

CH 3

C19H25NO4 MW: 331.41

C

272.2

226.2

122.1

331.2

0 50

100

Relative Int. (%)

100

150

200

85.1 N

300

350

Benzoylecgonine-d3, propyl derivative

I-16-C-ii

O

H O H

105.1

77.1

213.2

COOC 3H 7

CD 3

50

250

C19H22D3NO4 MW: 334.39

C

275.2

334.2

229.2

125.1

0 50

100

Relative Int. (%)

100

150

200

250 213.2

85.1 N

CD 3

50 110.1 82.1

COOC 3H 7 OD H O C H D

300

I-16-C-iii

350

Benzoylecgonine-d8, propyl derivative

D

C19H17D8NO4 MW: 339.35

D D

339.3

280.2

229.2

125.1

0 50

100

Relative Int. (%)

100

150

82.0

50

O

100

350

Benzoylecgonine, butyl derivative

I-16-D-i

C20H27NO4 MW: 345.43

C

240.1

122.0

345.1

272.1

166.0

0 150


300

H

77.0

200

250 227.1

CD 3 COOC 4H 9 N O H

85.1

O

50

250

224.1

CH 3 COOC 4H 9 N O H

105.0

50

200 m/z

300

I-16-D-ii

C20H24D3NO4 MW: 348.45

77.0 125.1

400

Benzoylecgonine-d3, butyl derivative

C

H

105.0

350

243.1

169.0

348.1

275.1

0 50

100

Relative Int. (%)

100

150

N

CD 3

110.0 82.1 125.1

100

COOC 4H 9 OD H O C H D

150

I-16-D-iii

350

400

Benzoylecgonine-d8, butyl derivative C20H19D8NO4 MW: 353.48

D D

243.1

200

250 m/z



300

D

169.0

0 50

250 227.1

85.1

50

200

280.1

300

353.2

350

400

120


Relative Int. (%)

100

CH 3 COOCH 2C 2F 5 N O H

82.1

50

Benzoylecgonine, pentafluoro-1-propoxy derivative

300.2

I-16-E-i

O

C19H20F5NO4 MW: 421.36 421.2

C

H

105.1

272.2

77.1

316.1

0 50

100

150

200

250

300

Relative Int. (%)

100

350

CD 3 COOCH 2C 2F 5 N O H

85.1

50

O

C19H17D3F5NO4 MW: 424.38

C

H

105.1

77.1

450

Benzoylecgonine-d3, pentafluoro-1-propoxy derivative

303.2

I-16-E-ii

400

275.2

424.2

319.1

0 50

100

150

200

250

300

Relative Int. (%)

100

350 303.2

85.1

I-16-E-iii

N

CD 3

50 110.1

COOCH 2C 2F 5 D OD H D O C H D D

82.1

280.2

400

450

Benzoylecgonine-d8, pentafluoro-1-propoxy derivative C19H12D8F5NO4 MW: 429.41 429.2

319.1

0 50

100

Relative Int. (%)

100

150

200

I-16-F-i N

CH 3

50

105.0

77.0

50

100

318.0

334.0

200

250

300

Relative Int. (%)

100 N

H O H

105.0

77.0

151.0

O

275.1

C19H19F6NO4 MW: 439.35 439.1

400

450

C19H16D3F6NO4 MW: 442.37 442.1

C

167.0

450

Benzoylecgonine-d3, hexafluoro-2-propoxy derivative

COOCH(CF3)2

CD 3

85.1

50

350 321.1

I-16-F-ii

400

Benzoylecgonine, hexafluoro-2-propoxy derivative

C

272.1

150

350

O

164.0

148.0

0

300

COOCH(CF3)2 H O H

82.0

250 m/z

337.0

0 50

100

Relative Int. (%)

100

150

200

I-16-F-iii N

50

CD 3

85.1 110.0 151.0

82.0

250

300

400

450

Benzoylecgonine-d8, hexafluoro-2-propoxy derivative

321.1

COOCH(CF3)2 D OD H O C D H D D

167.0

350

C19H11D8F6NO4 MW: 447.40 447.1 280.1

337.1

0 50

100

150

200

250 m/z



300

350

400

450

121


Relative Int. (%)

100

82.1 CH 3

N

COOSi(CH3)3 O H O

50

C19H27NO4Si MW: 361.51 361.2

C

H

105.1 73.1

Benzoylecgonine, trimethylsilyl derivative

I-16-G-i

240.2

256.2

122.1

346.2

0 50

100

Relative Int. (%)

100

150

200

85.1 CD 3

N

105.1 73.1

COOSi(CH3)3 H O H

50

250

300

400

Benzoylecgonine-d3, trimethylsilyl derivative

I-16-G-ii

243.2

O

350

C19H24D3NO4Si MW: 364.53

C

364.3

125.1

259.2

349.2

0 50

100

Relative Int. (%)

100

150

200

250

300

350

85.1 N

COOSi(CH3)3 D OD H O C D H D D

CD 3

50 110.1 73.1

Benzoylecgonine-d8, trimethylsilyl derivative

I-16-G-iii

243.2

400

C19H19D8NO4Si MW: 369.56

125.2

369.3

259.2

354.3

0 50

100

150

200

250

300

350

400


100

82.0 N

50

105.0 73.0

CH 3 COOSi(CH3)2C(CH3)3 O H O C H

Benzoylecgonine, t-butyldimethylsilyl derivative

I-16-H-i

346.1 403.2

204.0

122.0

179.0

C22H33NO4Si MW: 403.59

282.1

298.1


100

100

150

200

85.1 N

CD 3

105.0 73.0

COOSi(CH3)2C(CH3)3 H O H

50

179.0

125.1

250

O

C

300

350

400

450

Benzoylecgonine-d3, t-butyldimethylsilyl derivative

I-16-H-ii 285.1

349.1 207.0

C22H30D3NO4Si MW: 406.61 406.2

301.1


100

100

150

200

85.1 N

50

110.0 73.0

125.1

CD 3

250

COOSi(CH3)2C(CH3)3 D OD H D O C H D D

184.0

212.1

300

350

I-16-H-iii 285.1

400

450

Benzoylecgonine-d8, t-butyldimethylsilyl derivative 354.1

C22H25D8NO4Si MW: 411.64 411.2

301.1

0 50

100

150

200

250 m/z



300

350

400

450

122

Figure I-17. Mass spectra of ecgonine and its deuterated analogs (ecgonine-d3); (A) [TMS]2-underivatized; (B) [tBDMS]2-underivatized; (C) HFPoxy/TFA-derivatized; (D) PFPoxy/PFP-derivatized; (E) HFPoxy/HFB-derivatized.

Relative Int. (%)

100

83.1

I-17-A-i

CH

N

96.1

50

Ecgonine, di-trimethylsilyl derivative

3 COOSi(CH3)3

H OSi(CH3)3

73.0

C15H31NO3Si2 MW: 329.58

H

147.0

314.1

212.1

329.1

0 50

100

Relative Int. (%)

100

150

85.1

200

I-17-A-ii

CD

N

99.1

50

250

300

350

Ecgonine-d3, di-trimethylsilyl derivative

3 COOSi(CH3)3 H OSi(CH3)3

C15H28D3NO3Si2 MW: 332.60

H

73.0

215.1

147.0

332.1

317.1

0 50

100

Relative Int. (%)

100

150

200 m/z

250

300

82.1

I-17-B-i 50

73.0

CH

N

Ecgonine, di-t-butyldimethylsilyl derivative

3 COOSi(CH3)2C(CH3)3

H OSi(CH3)2C(CH3)3

356.2

H

96.1

350

275.1

C21H43NO3Si2 MW: 413.74 398.2 413.2

0 50

100

Relative Int. (%)

100

150

200

250

300

350

400

85.1 CD

I-17-B-ii 50

73.0

N

Ecgonine-d3, di-t-butyldimethylsilyl derivative

3 COOSi(CH3)2C(CH3)3

H OSi(CH3)2C(CH3)3

359.2

H

99.1

450

275.1

C21H40D3NO3Si2 MW: 416.76 401.2 416.3

0 50

Relative Int. (%)

100

100

150

250 m/z

300

350

318.0

I-17-C-i

CH

N

50

200

82.0

3 COOCH(CF3)2 H OOC–CF 3

400

450

Ecgonine (CAS NO.481-37-8), hexafluoro-2-propoxy/ trifluoroacetyl derivative C14H14F9NO4 MW: 447.24

H

94.0

431.0

264.0

0 50

100

150

200

250

300

Relative Int. (%)

100

I-17-C-ii

CD

N

50

350 321.0

85.1

3 COOCH(CF3)2

H OOC–CF 3

400

450

500

Ecgonine-d3, hexafluoro-2propoxy/trifluoroacetyl derivative C14H11D3F9NO4 MW: 450.22

H

97.1

434.0

267.0

0 50

100

150

200

250

300 m/z



350

400

450

500

123


Relative Int. (%)

100 CH

N

50

Ecgonine, pentafluoro-1propoxy/pentafluoropropionyl derivative

300.0

I-17-D-i

3 COOCH 2 C 2 F 5 H OOC–C 2 F 5

82.0

C15H17F10NO4 MW: 481.28

H

94.0

314.0

119.0

463.0

0 50

100

150

200

250

300

Relative Int. (%)

100

350

400

I-17-D-ii 50

CD

N

3 COOCH 2C 2F 5

H OOC–C 2 F 5

85.1

450

C15H14D3F10NO4 MW: 484.30 466.0

H

97.1

317.0

119.0

500

Ecgonine-d3, pentafluoro-1propoxy/pentafluoropropionyl derivative

303.1

0 50

100

150

200

250

300

350

400

450

500


100

318.0

I-17-E-i

CH

N

3 COOCH(CF3)2

H OOC–C 3 F 7

50 82.0

C16H14F13NO4 MW: 547.27

H

94.0

364.0

298.0

0 50

100

150

200

250

300


Ecgonine, hexafluoro-2propoxy/heptafluorobutyryl derivative

350

400

531.0

450

CD

N

50

3 COOCH(CF3)2

H OOC–C 3 F 7

600

C16H11D3F13NO4 MW: 550.28

H

85.1

550

Ecgonine-d3, hexafluoro-2propoxy/heptafluorobutyryl derivative

321.0

I-17-E-ii

500

97.0

367.0

301.0

534.1

0 50

100

150

200

250

300

350 m/z



400

450

500

550

600

124

Figure I-18. Mass spectra of anhydroecgonine methyl ester, and its deuterated analog (anhydroecgoninemethyl ester-d3).

Relative Int. (%)

100

152.0

I-18-i

CH 3 COOCH 3

N

Anhydroecgonine methyl ester (CAS NO.43021-26-7) C10H15NO2 MW: 181.23

50 181.1 82.1 57.1

94.0

122.1

166.0

138.0


100

100

150

200 155.0

I-18-ii N

Anhydroecgonine methyl ester-d3

CD 3 COOCH 3

C10H12D3NO2 MW: 184.25

50 184.1 85.1 60.1

97.1

125.1

141.0

169.1

0 50

100

150 m/z



200

125

Figure I-19. Mass spectra of caffeine, and its deuterated analog (caffeine-13C3).

Relative Int. (%)

100 H 3C

109.1

50 55.1

67.1

194.1

CH 3

O

I-19-i

Caffeine (CAS NO.58-08-2)

N

N

N

O

C8H10N4O2 MW: 194.19

N

CH 3

82.1

165.1

136.0

0 50

100

150

Relative Int. (%)

100

O

I-19-ii

H 3 13 C

50

111.1 57.1

68.1

84.1

13

200

N

N 13

Caffeine-13C3 13C

C5

N

N

O

250

197.1

CH 3

3H10N4O2 MW: 197.17

CH 3

138.1

168.1

0 50

100

150 m/z



200

250

126

Figure I-20. Mass spectra of methylphenidate, and its deuterated analog (methylphenidate-d3): (A) underivatized; (B) TFA-derivatized; (C) PFP-derivatized; (D) HFB-derivatized; (E) 4-CB-derivatized; (F) TMS-derivatized.

Relative Int. (%)

100

84.1

I-20-A-i

Methylphenidate (CAS NO.113-45-1) C14H19NO2 MW: 233.30

H N

50

CH C O CH 3

O

91.1

56.1

115.0

150.1

0 50

100

Relative Int. (%)

100

I-20-A-ii

150

200

250 Methylphenidate-d3

84.1

C14H16D3NO2 MW: 236.32

H

50

N

91.1

56.1

CH C O CD 3 O

115.1

153.1

0 50

100

150 m/z

Relative Int. (%)

100

200

F 3COC N

50 67.1

Methylphenidate, trifluoroacetyl derivative

180.1

I-20-B-i

C16H18F3NO3 MW: 329.31

CH C O CH 3 O

150.0

126.0

91.1

250

0 50

100

150

200

Relative Int. (%)

100

250

300

Methylphenidate-d3, trifluoroacetyl derivative

180.0

I-20-B-ii

F 3COC N

50

C16H15D3F3NO3 MW: 332.32

CH C O CD 3 O

67.1

91.1

350

153.1

126.0

0 50

100

150

200 m/z

Relative Int. (%)

100

300

F 5 C 2 OC CH C O CH 3 O

N

50 67.0

50

150.0

118.9

100

C17H18F5NO3 MW: 379.32

175.9

150

200

250

100

300

230.0

I-20-C-ii

N

67.0

CH C O CD 3 O

153.0

118.9

350

400

Methylphenidate-d3, pentafluoropropionyl derivative

F 5 C 2 OC

50

350

Methylphenidate, pentafluoropropionyl derivative

230.0

I-20-C-i

0

Relative Int. (%)

250

C17H15D3F5NO3 MW: 382.34

175.9

0 50

100

150

200

250 m/z



300

350

400

127


Relative Int. (%)

100

Methylphenidate, heptafluorobutyryl derivative

280.0

I-20-D-i

F 7 C 3 OC CH C O CH 3 O

N

50 55.1

91.0

115.0

150.0

169.0

C18H18F7NO3 MW: 429.33

226.0

0 50

100

150

200

250

300

Relative Int. (%)

100

350

400

280.0

I-20-D-ii

CH C O CD 3 O

N

55.1

91.1

115.0

Methylphenidate-d3, heptafluorobutyryl derivative

F 7 C 3 OC

50 153.1

169.0

450

C18H15D3F7NO3 MW: 432.35

226.0

0 50

100

150

200

250 m/z

300

Relative Int. (%)

100

334.2

N

100

150

250

300

350 334.2

N

91.1

C O CD 3 O

100

150

400

I-20-E-ii

250

100

300 m/z

I-20-F-i

350

400

3(H3C)Si N

84.1

500

550

C17H27NO2Si MW: 305.49

290.1

150


450

CH C O CH 3 O

0 100

Methylphenidate-d3, 4-carboethoxyhexafluorobutyryl derivative

Methylphenidate, trimethylsilyl derivative

73.1

50

550

441.1

156.1

50

500

C21H20D3F6NO5 MW: 486.42

306.1

200

450

288.1

195.0

0 50

CH

Methylphenidate, 4-carboethoxyhexafluorobutyryl derivative

438.1

H 5C2OOC3(F2C)OC

50

450

C21H23F6NO5 MW: 483.40

306.1

200

400

288.1

195.0

91.1

50

CH C O CH 3 O


I-20-E-i

H 5C2OOC3(F2C)OC

50

0

Relative Int. (%)

350

200

250

156.1

I-20-F-ii

350

Methylphenidate-d3, trimethylsilyl derivative 3(H3C)Si N

50

300

C17H24D3NO2Si MW: 308.51

CH C O CD 3 O

73.1 84.1

293.1

0 50

100

150

200 m/z



250

300

350

128

Figure I-21. Mass spectra of ritalinic acid, and its deuterated analog (ritalinic acid-d5): (A) 4-CB-derivatized; (B) [TMS]2-derivatized; (C) t-BDMS-derivatized. Relative Int. (%)

100

334.1

I-21-A-i CH–C–OH

50

H 5C 2OOC(F2C)3OC– N

O

50

100

150

200

100

I-21-A-ii

D D

50

50

100

150

300

452.1

350

400

334.1

450

200

O

C20H16D5F6NO5 MW: 474.41

288.0 306.1

250

300

500

Ritalinic acid-d5, 4-carboethoxyhexafluorobutyryl derivative

D

D CH–C–OH

H 5C 2OOC(F2C)3OC– N

96.1

0

250 D

C20H21F6NO5 MW: 469.37

288.0 306.1

91.1

0

Relative Int. (%)

Ritalinic acid (CAS NO.19395-41-6) 4-carboethoxyhexafluorobutyryl derivative

457.2

350

400

450

500

m/z Relative int. (%)

100

Ritalinic acid, di-trimethylsilyl derivative

156.1

I-21-B-i

50

O

(H3C)3Si– N

84.1

265.0

0 50

100

150

100 Relative int. (%)

C19H33NO2Si2 MW: 363.64

CH–C–OSi(CH3)3

73.1

200

250

300

350

Ritalinic acid-d5, di-trimethylsilyl derivative

156.1

I-21-B-ii

D

50

D

73.1

D

D

O

270.1

0 50

100

150

C19H28D5NO2Si2 MW: 368.67

D CH–C–OSi(CH3)3

(H3C)3Si– N

84.1

200

400

250

300

350

400


100

193.1

I-21-C-i

Ritalinic acid, t-butyldimethylsilyl derivative CH–C–OH

50

75.1

(H3C)3C(H3C)2Si– N

91.1

137.0

C19H31NO2Si MW: 333.54

O

165.1

0 50

100

150

200

Relative Int. (%)

100

198.1

I-21-C-ii 50

250 D D

75.1 96.1

142.1

300 D

Ritalinic acid-d5, t-butyldimethylsilyl derivative

D CH–C–OH

(H3C)3C(H3C)2Si– N

170.1

D

350

C19H26D5NO2Si MW: 338.57

O

0 50

100

150

200 m/z



250

300

350

129

Summary of Drugs, Isotopic Analogs, and Chemical Derivatization Groups Included in Figure II (Opioids) Compound

Isotopic analog


Figure #

Heroin

d3, d9

None (3)

II-1

6-Acetylmorphine

d3, d6

None, acetyl, TFA, propionyl, PFP, HFB, TMS, t-BDMS (24)

II-2

Morphine

d3, d6

Ethyl, propyl, butyl, [acetyl]2, [TFA]2, propionyl, [propionyl]2, [PFP]2, [HFB]2, [TMS]2, t-BDMS, [t-BDMS]2, ethyl/acetyl, ethyl/TMS, propyl/TMS, propyl/t-BDMS, butyl/TMS, butyl/t-BDMS, acetyl/TMS, acetyl/t-BDMS, propionyl/TMS (63)

II-3

Hydromorphone

d3, d6

Acetyl, [acetyl]2, [TFA]2, propionyl, PFP, [PFP]2, HFB, [HFB]2, TMS, [TMS]2, t-BDMS, [t-BDMS]2, MA/ethyl, MA/acetyl, MA/propionyl, MA/TMS, MA/t-BDMS, HA/[TMS]2 (54)

II-4

Oxymorphone

d3

[acetyl]2, [acetyl]3, [TFA]2, propionyl, [propionyl]2, [propionyl]3, [PFP]2, [HFB]2, [TMS]2, [TMS]3, t-BDMS, MA/ethyl, MA/acetyl, MA/[acetyl]2, MA/propionyl, MA/[HFB]2, MA/ [TMS]2, MA/[t-BDMS]2, MA/ethyl/propionyl, MA/ethyl/TMS, MA/ethyl/t-BDMS, MA/acetyl/ TMS, MA/propionyl/TMS, HA/[TMS]3, HA/[ethyl]2/propionyl, HA/[ethyl]2/TMS (52)

II-5

6-Acetylcodeine

d3

None (2)

II-6

13C

Codeine

d3, d6,


II-7

Hydrocodone

d3, d6

1d3

None, ethyl, acetyl, TMS, t-BDMS, MA, HA/TMS (21)

II-8

Dihydrocodeine

d3, d6


II-9

Oxycodone

d3, d6

None, acetyl, [acetyl]2, propionyl, TMS, [TMS]2, t-BDMS, [t-BDMS]2, MA, MA/propionyl, MA/TMS, HA/[propionyl]2, HA/[TMS]2, HA/ethyl/propionyl (42)

II-10

Noroxycodone

d3

None, [acetyl]2, [TFA]3, propionyl, [PFP]2, [HFB]2, [TMS]2, [TMS]3, MA/ethyl, MA/acetyl, MA/[TFA]2, MA/propionyl, MA/PFP, MA/[HFB]2, MA/[TMS]2, MA/t-BDMS, MA/ethyl/ propionyl, MA/ethyl/TMS, MA/ethyl/t-BDMS, MA/acetyl/TMS, MA/propionyl/TMS, HA/[ethyl]2/TMS (44)

II-11

Buprenorphine

d4

Methyl, ethyl, acetyl, MBTFA, PFP, HFB, TMS, [TMS]2, t-BDMS (18)

II-12

Norbuprenorphine

d3

[Methyl]2, [ethyl]2, [acetyl]2, [MBTFA]2, [PFP]2, [HFB]2, [TMS]2, [TMS]3, t-BDMS (18)

II-13

Fentanyl

d5

None (2)

II-14

Norfentanyl

d5

None, acetyl, TCA, TFA, PFP, HFB, 4-CB, TMS, t-BDMS (18)

II-15

Methadone

d3, d9

None (3)

II-16

EDDP

d3

None (2)

II-17

Propoxyphene

d5, d7, d11

None (4)

II-18

Norpropoxyphene

d5

None (2)

II-19

Meperidine

d4

None (2)

II-20

Normeperidine

d4

None, ethyl, propyl, butyl, acetyl, TCA, TFA, PFP, HFB, 4-CB, TMS, t-BDMS (24)

II-21


Figure II — Opioids


131

Appendix One — Figure II Mass Spectra of Commonly Abused Drugs and Their Isotopically Labeled Analogs in Various Derivatization Forms — Opioids Figure II-1. Mass spectra of heroin and its deuterated analogs (heroin-d3, -d9) ......................................................................... 133 Figure II-2. Mass spectra of 6-acetylmorphine and its deuterated analogs (6-acetylmorphine-d3, -d6): (A) underivatized; (B) acetyl-derivatized; (C) TFA-derivatized; (D) propionyl-derivatized; (E) PFP-derivatized; (F) HFB-derivatized; (G); (H) TMS-derivatized; (I) t-BDMS-derivatized ............................................................................................................................ 134 Figure II-3. Mass spectra of morphine and its deuterated analogs (morphine-d3, -d6): (A) ethyl-derivatized; (B) propylderivatized; (C) butyl-derivatized; (D) [acetyl]2-derivatized; (E) [TFA]2-derivatized; (F) propionyl-derivatized; (G) [propionyl]2-derivatized; (H) [PFP]2-derivatized; (I) [HFB]2-derivatized; (J) [TMS]2-derivatized; (K) t-BDMS-derivatized; (L) [t-BDMS]2-derivatized; (M) ethyl/acetyl-derivatized; (N) ethyl/TMS-derivatized; (O) propyl/TMS-derivatized; (P) propyl/t-BDMS-derivatized; (Q) butyl/TMS-derivatized; (R) butyl/t-BDMS-derivatized; (S) acetyl/TMS-derivatized; (T) acetyl/t-BDMS-derivatized; (U) propionyl/TMS-derivatized ...................................................................................................... 138 Figure II-4. Mass spectra of hydromorphone and its deuterated analogs (hydromorphone-d3, -d6): (A) acetyl-derivatized; (B) [acetyl]2-derivatized; (C) [TFA]2-derivatized; (D) propionyl-derivatized; (E) PFP-derivatized; (F) [PFP]2-derivatized; (G) HFB-derivatized (H) [HFB]2-derivatized; (I) TMS-derivatized; (J) [TMS]2-derivatized; (K) t-BDMS-derivatized; (L) [t-BDMS]2-derivatized; (M) MA/ethyl-derivatized; (N) MA/acetyl-derivatized; (O) MA/propionyl-derivatized; (P) MA/ TMS-derivatized; (Q) MA/t-BDMS-derivatized; (R) HA/[TMS]2-derivatized ........................................................................... 149 Figure II-5. Mass spectra of oxymorphone and its deuterated analogs (oxymorphone-d3): (A) [acetyl]2-derivatized; (B) [acetyl]3-derivatized; (C) [TFA]2-derivatized; (D) propionyl-derivatized; (E) [propionyl]2-derivatized; (F) [propionyl]3derivatized; (G) [PFP]2-derivatized; (H) [HFB]2-derivatized; (I) [TMS]2-derivatized; (J) [TMS]3-derivatized; (K) t-BDMSderivatized; (L) MA/ethyl-derivatized; (M) MA/acetyl-derivatized; (N) MA/[acetyl]2-derivatized; (O) MA/propionylderivatized; (P) MA/[HFB]2-derivatized; (Q) MA/[TMS]2-derivatized; (R) MA/[t-BDMS]2-derivatized; (S) MA/ethyl/ propionyl-derivatized; (T) MA/ethyl/TMS-derivatized; (U) MA/ethyl/t-BDMS-derivatized; (V) MA/acetyl/TMS-derivatized; (W) MA/propionyl/TMS; (X) HA/[TMS]3/propionyl-derivatized; (Y) HA/[ethyl]2HA/[ethyl]2/TMS-derivatized; (Z) HA/ [ethyl]2/TMS-derivatized .............................................................................................................................................................. 158 Figure II-6. Mass spectra of 6-acetylcodeine and its deuterated analogs (6-acetylcodeine-d3) ................................................. 167 Figure II-7. Mass spectra of codeine and its deuterated analogs (codeine-d3, -d6, 13C1-d3): (A) underivatized; (B) acetylderivatized; (C) TFA-derivatized; (D) propionyl-derivatized; (E) PFP-derivatized; (F) HFB-derivatized; (G) TMSderivatized; (H) t-BDMS-derivatized. .......................................................................................................................................... 168 Figure II-8. Mass spectra of hydrocodone and its deuterated analogs (hydrocodone-d3, -d6): (A) underivatized; (B) ethylderivatized; (C) acetyl-derivatized; (D) TMS-derivatized; (E) t-BDMS-derivatized; (F) MA-derivatized; (G) HA/TMSderivatized ..................................................................................................................................................................................... 174 Figure II-9. Mass spectra of dihydrocodeine and its deuterated analogs (dihydrocodeine-d3, -d6): (A) underivatizedderivatized; (B) acetyl-derivatized; (C) TFA-derivatized; (D) propionyl-derivatized; (E) PFP-derivatized; (F) HFBderivatized; (G) TMS-derivatized; (H) t-BDMS-derivatized ....................................................................................................... 178 Figure II-10. Mass spectra of oxycodone and its deuterated analogs (oxycodone-d3, -d6): (A) underivatized; (B) acetylderivatized; (C) [acetyl]2-derivatized; (D) propionyl-derivatized; (E) TMS-derivatized; (F) [TMS]2-derivatized; (G) tBDMS-derivatized; (H) [t-BDMS]2-derivatized; (I) MA-derivatized; (J) MA/propionyl-derivatized; (K) MA/TMSderivatized; (L) HA/[propionyl]2-derivatized; (M) HA/[TMS]2-derivatized; (N) HA/ethyl/propionyl-derivatized .................. 182 Figure II-11. Mass spectra of noroxycodone and its deuterated analogs (noroxycodone-d3): (A) underivatized; (B) [acetyl]2-derivatized; (C) [TFA]3-derivatized; (D) propionyl-derivatized; (E) [PFP]2-derivatized; (F) [HFB]2-derivatized; (G) [TMS]2-derivatized; (H) [TMS]3-derivatized; (I) MA/ethyl-derivatized; (J) MA/acetyl-derivatized; (K) MA/[TFA]2derivatized; (L) MA/propionyl-derivatized; (M) MA/PFP-derivatized; (N) MA/[HFB]2-derivatized; (O) MA/[TMS]2derivatized; (P) MA/t-BDMS-derivatized; (Q) MA/ethyl/propionyl-derivatized; (R) MA/ethyl/TMS-derivatized; (S) MA/ ethyl/t-BDMS-derivatized; (T) MA/acetyl/TMS-derivatized; (U) MA/propionyl/TMS-derivatized; (V) HA/[ethyl]2/TMSderivatized ..................................................................................................................................................................................... 189 Figure II-12. Mass spectra of buprenorphine and its deuterated analogs (buprenorphine-d4): (A) methyl-derivatized; (B) ethyl-derivatized; (C) acetyl-derivatized; (D) MBTFA-derivatized; (E)PFP-derivatized; (F) HFB-derivatized; (G) TMSderivatized; (H) [TMS]2-derivatized; (I) t-BDMS-derivatized ................................................................................................... 197 Figure II-13. Mass spectra of norbuprenorphine and its deuterated analogs (norbuprenorphine-d3): (A) [methyl]2derivatized; (B) [ethyl]2-derivatized; (C) [acetyl]2-derivatized; (D) [MBTFA]2-derivatized; (E) [PFP]2-derivatized; (F) [HFB]2-derivatized; (G) [TMS]2-derivatized; (H) [TMS]3-derivatized; (I) t-BDMS-derivatized ............................................. 200 Figure II-14. Mass spectra of fentanyl and its deuterated analogs (fentanyl-d5) ........................................................................ 203 Figure II — Opioids


132

Figure II-15. Mass spectra of norfentanyl and its deuterated analogs (norfentanyl-d5): (A) underivatized; (B) acetylderivatized; (C) TCA-derivatized; (D) TFA-derivatized; (E) PFP-derivatized; (F) HFB-derivatized; (G) 4-CB-derivatized; (H) TMS-derivatized; (I) t-BDMS-derivatized ............................................................................................................................ 204 Figure II-16. Mass spectra of methadone and its deuterated analogs (methadone-d3, -d9) ........................................................ 207 Figure II-17. Mass spectra of EDDP and its deuterated analogs (EDDP-d3) ............................................................................. 208 Figure II-18. Mass spectra of propoxyphene and its deuterated analogs (propoxyphene-d5, -d7, -d11) ..................................... 209 Figure II-19. Mass spectra of norpropoxyphene and its deuterated analogs (norpropoxyphene-d5) .......................................... 210 Figure II-20. Mass spectra of meperidine and its deuterated analogs (meperidine-d4) .............................................................. 211 Figure II-21. Mass spectra of normeperidine and its deuterated analogs (normeperidine-d4): (A) underivatized-derivatized; (B) ethyl-derivatized; (C) propyl-derivatized; (D) butyl-derivatizedacetyl; (E) acetyl-derivatized; (F) TCA-derivatized; (G) TFA-derivatized; (H) PFP-derivatized; (I) HFB-derivatized; (J) 4-CB-derivatized; (K) TMS-derivatized; (L) t-BDMSderivatized ..................................................................................................................................................................................... 212



133

Figure II-1. Mass spectra of heroin and its deuterated analogs (heroin-d3, -d9). Relative Int. (%)

100

Heroin (CAS NO. 561-27-3)

H3C-COO O

C21H23NO5 MW: 369.41

50

81.0

-

204.0

310.1

215.0

162.0

146.0

369.1 268.1

N CH 3

H3C-COO

124.0

327.1

II-1-i

284.1


100

100

150

Heroin-d3

H3C-COO

C21H20D3NO5 MW: 372.43

50

200

127.0

-

N CD 3

207.0

350

400

330.1 372.1 271.1

313.1

218.0

165.0

149.0

300

II-1-ii

O H3C-COO

81.0

250

287.1


100

100

150

200

D3C-COO

Heroin-d9 C21H14D9NO5 MW: 378.47

II-1-iii

O

50

-

128.1 149.1

300

350

400

334.2 272.1

378.2

316.2

N CD 3

D3C-COO

81.0

250

210.1

219.1

166.1

288.1

0 50

100

150

200

250 m/z



300

350

400

134

Figure II-2. Mass spectra of 6-acetylmorphine and its deuterated analogs (6-acetylmorphine-d3, -d6): (A) underivatized; (B) acetyl-derivatized; (C) TFA-derivatized; (D) propionyl-derivatized; (E) PFP-derivatized; (F) HFB-derivatized; (G) TMS-derivatized; (H) t-BDMS-derivatized. Relative Int. (%)

100

HO

6-Acetylmorphine (CAS NO. 2784-73-8)

O

C19H21NO4 MW: 327.37

50

57.1

H 3C–COO

146.1

124.1

81.0

174.1

268.1

II-2-A-i

327.1

-

N CH 3

215.1

211.0


100

100

150

200

6-Acetylmorphine-d3 (CAS NO. 136765-25-8)

73.1

300

HO O

C19H18D3NO4 MW: 330.39

50

250

H 3C–COO

207.0

149.1

127.1

97.1

271.1

350 330.1

II-2-A-ii

-

N CD 3

218.1

174.0


100

100

150

200

O

C19H15D6NO4 MW: 333.41

D 3C–COO

149.1 73.1

300 271.1

HO

6-Acetylmorphine-d6 (CAS NO. 152477-90-2)

50

250

128.1

97.1

174.0

350

II-2-A-iii

333.2

-

N CD 3

218.1

210.1

0 50

Relative Int. (%)

100

100

6-Acetylmorphine, acetyl derivative

81.1

200 m/z

250

300

327.1

H 3C–COO

268.1

O

C21H23NO5 MW: 369.41

50

150

162.1

124.1 146.1

II-2-B-i 369.2

310.1

-

N CH 3

H 3C–COO

350

215.1

204.1


100

100

150

6-Acetylmorphine-d3, acetyl derivative C21H20D3NO5 MW: 372.43

50

81.1

200

H 3C–COO

149.1

300

350 330.2

H 3C–COO

271.1

O

127.1

250

-

N CD 3

165.1 207.1

II-2-B-ii

400

372.2

313.1 218.1


100

100

150

6-Acetylmorphine-d6, acetyl derivative

81.1

300

H 3C–COO

149.1

350

-

N CD 3

210.1

400

II-2-B-iii

271.1

D 3C–COO

128.1

250

333.2

O

C21H17D6NO5 MW: 375.45

50

200

375.2 313.2

218.1

166.1

0 50

100

150

200

250 m/z



300

350

400

135

Figure II-2. (Continued) Relative Int. (%)

100

6-Acetylmorphine, trifluoroacetyl derivative

F 3C–COO O

C21H20F3NO5 MW: 423.38

50

II-2-C-i

423.1

-

N CH 3

H 3C–COO

311.0

204.1 81.1

162.1

124.1

364.1

380.0


100

100

150

200

250

6-Acetylmorphine-d3, trifluoroacetyl derivative

II-2-C-ii

O

400

450

367.1 426.1

-

N CD 3

H 3C–COO

207.1 165.1

127.1

81.1

350

F 3C–COO

C21H17D3F3NO5 MW: 426.40

50

300

314.1 383.1


100

100

150

200

250

6-Acetylmorphine-d6, trifluoroacetyl derivative

II-2-C-iii

O

450

429.1

-

314.1

166.1

128.1

400 367.1

N CD 3

D 3C–COO

210.1 81.1

350

F 3C–COO

C21H14D6F3NO5 MW: 429.42

50

300

383.1

0 50

Relative Int. (%)

100

100

150

200

6-Acetylmorphine, propionyl derivative

57.1

81.1

300

H 5C 2–COO

-

N CH 3

H 3C–COO

400

450

327.1

268.1

383.1

215.1

204.1

146.1

350

II-2-D-i

O

C22H25NO5 MW: 383.44

50

250 m/z


100

100

150

6-Acetylmorphine-d3, propionyl derivative

57.1

250

H 5C 2–COO

-

N CD 3

H 3C–COO

350

400

330.1

386.2

271.1

218.1

207.1 81.1

300

II-2-D-ii

O

C22H22D3NO5 MW: 386.46

50

200

149.1


100

100

150

6-Acetylmorphine-d6, propionyl derivative

81.1

300

II-2-D-iii

O

-

N CD 3

D 3C–COO

210.1 57.1

250

H 5C 2–COO

C22H19D6NO5 MW: 389.47

50

200

350

400

333.2

271.1

389.2

218.1

149.1

0 50

100

150

200

250 m/z



300

350

400

136


100

6-Acetylmorphine, pentafluoropropionyl derivative

O

C22H20F5NO5 MW: 473.39

50

81.1

II-2-E-i

F 5 C 2 –COO

204.1

119.0

414.1 473.1

-

N CH 3

H 3C–COO

361.0 430.1

162.1


100

100

150

200

250

6-Acetylmorphine-d3, pentafluoropropionyl derivative

81.1

350

O

207.1

400

II-2-E-ii

F 5 C 2 –COO

C22H17D3F5NO5 MW: 476.41

50

300

500

417.1 476.1

-

N CD 3

H 3C–COO

364.0

165.1

119.0

450

433.1


100

100

150

200

250

6-Acetylmorphine-d6, pentafluoropropionyl derivative

73.1

400

II-2-E-iii

O

210.1

119.0

350

F 5 C 2 –COO

C22H14D6F5NO5 MW: 479.43

50

300

450

479.1

-

N CD 3

D 3C–COO

500

417.1

364.0

166.1

433.1

0 50

100

150

200

250

300

350

400

450

500


100

6-Acetylmorphine, heptafluorobutyryl derivative

81.1

H 3C–COO

204.1

124.1

II-2-F-i

O

C23H20F7NO5 MW: 523.40

50

464.1

F 7 C 3 –COO

-

N CH 3

523.1 411.0

169.0

480.1


100

100

150

200

250

6-Acetylmorphine-d3, heptafluorobutyryl derivative

81.1

127.1

350

O

207.1

H 3C–COO

165.1

400

450

II-2-F-ii

F 7 C 3 –COO

C23H17D3F7NO5 MW: 526.42

50

300

500

550

467.1

526.1

-

N CD 3

414.1 483.1


100

100

150

200

250

6-Acetylmorphine-d6, heptafluorobutyryl derivative

81.1

128.1

350

O

210.1

D 3C–COO

400

450

II-2-F-iii

F 7 C 3 –COO

C23H14D6F7NO5 MW: 529.43

50

300

500

550

467.1

529.2

-

N CD 3

414.1

169.0

483.1

0 50

100

150

200

250

300 m/z

350



400

450

500

550

137


100

6-Acetylmorphine, trimethylsilyl derivative

II-2-G-i

O

C22H29NO4Si MW: 399.56

50

399.1

(H3C)3Si–O

H 3C–COO

73.1

287.1 204.1

124.1

340.1

-

N CH 3

266.0

324.1


100

100

150

200

6-Acetylmorphine-d3, trimethylsilyl derivative

350

400

450 402.2

343.1

O

-

N CD 3

H 3C–COO

207.1

127.1

300

II-2-G-ii

(H3C)3Si–O

C22H26D3NO4Si MW: 402.57 73.1

50

250

290.1 327.1

266.0


100

100

150

200

6-Acetylmorphine-d6, trimethylsilyl derivative

(H3C)3Si–O

D 3C–COO

350

400

450 405.2

343.1

-

N CD 3

290.1 210.1

128.1

300

II-2-G-iii

O

C22H23D6NO4Si MW: 405.59 73.1

50

250

327.1

266.0

0 50

Relative Int. (%)

100

100

150

6-Acetylmorphine, t-butyldimethylsilyl derivative

50

200

250 m/z

450

441.3

-

N CH 3

384.2

267.1

204.1

162.1

400

II-2-H-i

O H 3C–COO

350

342.2

(H3C)3C(H3C)2Si–O

C25H35NO4Si MW: 441.64 73.1

300

324.1


100

100

150

6-Acetylmorphine-d3, t-butyldimethylsilyl derivative

50

200

250

300

(H3C)3C(H3C)2Si–O

II-2-H-ii

O

C25H32D3NO4Si MW: 444.65 73.1

H 3C–COO

400

450

500

345.2 444.3

-

N CD 3

387.2

267.1

207.1

165.1

350

327.2


100

100

150

6-Acetylmorphine-d6, t-butyldimethylsilyl derivative

200

300

(H3C)3C(H3C)2Si–O

II-2-H-iii

O

C25H29D6NO4Si MW: 447.67 73.1

50

250

D 3C–COO

450

500

447.3

-

267.1

400

346.2

N CD 3

210.1

149.1

350

390.2 327.2

0 50

100

150

200

250

300 m/z



350

400

450

500

138

Figure II-3. Mass spectra of morphine and its deuterated analogs (morphine-d3, -d6): (A) ethyl-derivatized; (B) propylderivatized; (C) butyl-derivatized; (D) [acetyl]2-derivatized; (E) [TFA]2-derivatized; (F) propionyl-derivatized; (G) [propionyl]2-derivatized; (H) [PFP]2-derivatized; (I) [HFB]2-derivatized; (J) [TMS]2-derivatized; (K) t-BDMSderivatized; (L) [t-BDMS]2-derivatized; (M) ethyl/acetyl-derivatized; (N) ethyl/TMS-derivatized; (O) propyl/TMSderivatized; (P) propyl/t-BDMS-derivatized; (Q) butyl/TMS-derivatized; (R) butyl/t-BDMS-derivatized; (S) acetyl/ TMS-derivatized; (T) acetyl/t-BDMS-derivatized; (U) propionyl/TMS-derivatized. Relative Int. (%)

100

Morphine (CAS NO. 57-27-2), ethyl derivative

H 5 C 2 –O

O

C19H23NO3 MW: 313.39

50 57.1

97.1

HO

162.1

-

N CH 3

214.1

124.1

313.2

II-3-A-i 243.1

256.1

284.1

0 50

100

Relative Int. (%)

100

150

200

Morphine-d3 (CAS NO. 67293-88-3), ethyl derivative

57.1

97.1

300

165.1

HO

127.1

350 316.2

II-3-A-ii

H 5 C 2 –O O

C19H20D3NO3 MW: 316.41

50

250

-

N CD 3

217.1

246.1 256.2

287.2

0 50

100

Relative Int. (%)

100

150

200

Morphine-d6, ethyl derivative

H 5 C 2 –O

DD

O

C19H17D6NO3 57.1 MW: 319.43 97.1

50

250

168.1

HO

300

350 319.2

II-3-A-iii

D

-

N CD 3

220.1

127.1

249.2

256.2

290.2

0 50

100

Relative Int. (%)

100

150

200 m/z

Morphine, propyl derivative

-

N CH 3

214.1

124.1

81.1

59.1

HO

350

II-3-B-i

O

162.1

300

327.2

H 7 C 3 –O

C20H25NO3 MW: 327.42

50

250

284.1 257.1

270.1

310.2

0 50

100

Relative Int. (%)

100

150

200

Morphine-d3, propyl derivative

62.1

HO

127.1

81.1

350

II-3-B-ii

O

165.1

300

330.2

H 7 C 3 –O

C20H22D3NO3 MW: 330.44

50

250

-

N CD 3

217.1

260.2

270.1

287.1

313.2

0 50

100

Relative Int. (%)

100

150

Morphine-d6, propyl derivative

H 7 C 3 –O

O

C20H19D6NO3 MW: 333.45

50 65.1

168.1

HO

250

300

350 333.2

DD

II-3-B-iii

D

-

N CD 3

220.1

128.1

81.1

200

263.2

290.2 270.1

316.2

0 50


100

150


250

300

350

139


100

H 9 C 4 –O

Morphine, butyl derivative

O

C21H27NO3 MW: 341.44

50

59.1

81.1

II-3-C-i

162.1

341.2

-

N CH 3

HO

284.1 124.1

214.1

271.1

324.2


100

100

150

200

81.1

II-3-C-ii

O

C21H24D3NO3 MW: 344.46 62.1

300

H 9 C 4 –O

Morphine-d3, butyl derivative

50

250

165.1

400

350

400

350

400

344.2

-

N CD 3

HO

127.1

350

287.1

217.1

327.2

274.2


100

100

150

200

Morphine-d6, butyl derivative

H 9 C 4 –O

65.1

81.1

DD

168.1

300

II-3-C-iii -

N CD 3

HO

220.1

128.1

347.2

D

O

C21H21D6NO3 MW: 347.48

50

250

277.2

290.2 330.2

0 50

100

150

200

250

300


100

Morphine, di-acetyl derivative C21H23NO5 MW: 369.41

50

81.1

H 3C–COO

II-3-D-i

O

369.2

268.1

-

310.1

N CH 3

H 3C–COO

327.1

204.1

215.1

146.1

124.1


100

100 Morphine-d3, di-acetyl derivative C21H20D3NO5 MW: 372.43

50

81.1

150

200

250

H 3C–COO

II-3-D-ii

O

271.1

-

N CD 3

H 3C–COO

127.1 149.1

300

207.1

350

400

330.2 372.2

313.2

218.1

165.1


100

100 Morphine-d6, di-acetyl derivative C21H17D6NO5 MW: 375.45

50

81.1

150

200

H 3C–COO O H 3C–COO

152.1 128.1

DD

250

300

II-3-D-iii

D

274.2

-

N CD 3

210.1

350

400

333.2 375.2

316.2

221.1

168.1

0 50

100

150

200

250 m/z



300

350

400

140


100

Morphine, di-trifluoroacetyl derivative

50

O

C21H17F6NO5 MW: 477.35 69.0

364.1

F 3C–COO

II-3-E-i

-

N CH 3

F 3C–COO

477.1 307.0

115.1

0 50

100

Relative Int. (%)

100

150

200

Morphine-d3, di-trifluoroacetyl derivative

50

250

300

350

400 367.1

F 3C–COO O

C21H14D3F6NO5 MW: 480.37 69.0 115.1

450

II-3-E-ii

-

N CD 3

F 3C–COO

500

480.1 307.0

0 50

100

Relative Int. (%)

100

50

0

150

200

250

F 3C–COO

C21H11D6F6NO5 MW: 483.39 69.1 115.1

F 3C–COO

50

100

300

350

400

450

370.1

Morphine-d6, di-trifluoroacetyl derivative

DD

500

II-3-E-iii

D

O

-

N CD 3

483.1 317.1

150

200

250

300

350

400

450

500


100

Morphine, propionyl derivative C20H23NO4 MW: 341.40

50

O HO

146.1

57.1

81.1

124.1

341.1

268.1

H 5C 2–COO

II-3-F-i

-

N CH 3

215.1

162.1

284.1

0 50

100

Relative Int. (%)

100

150

Morphine-d3, propionyl derivative

200

57.1

81.1

149.1 127.1

350

400

II-3-F-ii

271.1

O HO

300 344.2

H 5C 2–COO

C20H20D3NO4 MW: 344.42

50

250

-

N CD 3

218.1

165.1

287.1

0 50

100

Relative Int. (%)

100

150

Morphine-d6, propionyl derivative

200 H 5C 2–COO

C20H17D6NO4 MW: 347.44

50

O

HO

152.1 57.1

81.1

128.1

250 DD

300

350 347.2

274.2

400

II-3-F-iii

D

-

N CD 3

221.1

168.1

290.1

0 50

100

150

200

250 m/z



300

350

400

141


100

Morphine, di-propionyl derivative

O

C23H27NO5 MW: 397.46

50

341.1

H 5C 2–COO

-

H 5C 2–COO

II-3-G-i

268.1

N CH 3

397.2 324.1

218.1

57.1 81.1

162.1

146.1


100

100

150

Morphine-d3, di-propionyl derivative

57.1

250

350

-

H 5C 2–COO

II-3-G-ii 400.2

271.1

N CD 3

450

327.1

221.1

165.1

149.1

400

344.1

O

81.1

300

H 5C 2–COO

C23H24D3NO5 MW: 400.48

50

200


100

100

150

Morphine-d6, di-propionyl derivative

250

H 5C 2–COO O

C23H21D6NO5 MW: 403.50

50

200

300

400

347.2 DD

274.2

N CD 3

450

II-3-G-iii

D

-

H 5C 2–COO

350

403.2

330.2

224.2

57.1

81.1

168.1

152.1

0 50

Relative Int. (%)

100

50

100

150

200

250 m/z

300

350

400

414.1

Morphine, di-pentafluoropropionyl derivative

F 5 C 2 –COO

C23H17F10NO5 MW: 577.37 119.0

F 5 C 2 –COO

O

450

II-3-H-i

-

N CH 3

577.1 430.1

357.0


100

100

150

200

Morphine-d3, di-pentafluoropropionyl derivative

300

350

400

450

500

417.1 O F 5 C 2 –COO

550

600

II-3-H-ii

F 5 C 2 –COO

C23H14D3F10NO5 MW: 580.39 119.0

50

250

-

N CD 3

580.1 357.0

433.1


100

50

100

150

200

250

300

350

400

450

500

420.1

Morphine-d6, di-pentafluoropropionyl derivative

F 5 C 2 –COO

C23H11D6F10NO5 MW: 583.41 119.0

F 5 C 2 –COO

DD

O

550

600

II-3-H-iii

D

-

N CD 3

583.1 367.1

436.1

0 50

100

150

200

250

300

350 m/z



400

450

500

550

600

142


100

Morphine, di-heptafluorobutyryl derivative

O

C25H17F14NO5 MW: 677.38

50

F 7 C 3 –COO

464.1

II-3-I-i

F 7 C 3 –COO

-

N CH 3

169.0

69.0

677.1

480.1


100

100

150

200

250

Morphine-d3, di-heptafluorobutyryl derivative

350

400

O

F 7 C 3 –COO

450

550

600

650

700

-

N CD 3

169.0

69.0

500 467.1

II-3-I-ii

F 7 C 3 –COO

C25H14D3F14NO5 MW: 680.40

50

300

680.1

483.1


100

100

150

200

250

Morphine-d6, di-heptafluorobutyryl derivative

F 7 C 3 –COO

350 DD

F 7 C 3 –COO

400

450

500

550

600

650

D

-

N CD 3

683.1

169.0

69.0

700

470.1

II-3-I-iii

O

C25H11D6F14NO5 MW: 683.42

50

300

486.1

0 50

100

150

200

250

300

350

400

450

500

550

600

650

700


100

Morphine, 73.1 di-trimethylsilyl derivative

-

N CH 3

(H3C)3Si– O

196.1

146.0

429.2

O

236.1

C23H35NO3Si2 MW: 429.70

50

(H3C)3Si– O

II-3-J-i

287.1

414.1

401.1

324.1

0 50

100

Relative Int. (%)

100 73.1

150

250

300

Morphine-d3, di-trimethylsilyl derivative C23H32D3NO3Si2 MW: 432.72

50

200

400

O

239.1

-

N CD 3

(H3C)3Si– O

290.1

450 432.2

(H3C)3Si– O

II-3-J-ii 199.1

149.1

350

417.2 404.1

327.1

0 50

100

Relative Int. (%)

100 73.1

150

Morphine-d6, di-trimethylsilyl derivative C23H29D6NO3Si2 MW: 435.74

50

200

250

300

II-3-J-iii 200.1

DD

O

293.1

400

450 435.2

(H3C)3Si– O

239.1 149.1

350 D

-

N CD 3

(H3C)3Si– O

420.2 404.1

330.1

0 50

100

150

200

250 m/z



300

350

400

450

143


100

(H3C)3C(H3C)2Si–O

Morphine, t-butyldimethylsilyl derivative

O

C23H33NO3Si MW: 399.60

50

HO

162.1

73.1

-

399.2

N CH 3

229.1

216.1

124.1

342.2

II-3-K-i

272.1

285.1

329.2


100

100

150

200

250

(H3C)3C(H3C)2Si–O

Morphine-d3, t-butyldimethylsilyl derivative

HO

165.1

400

450

345.2

-

402.3

N CD 3

229.1

216.1

127.1

350

II-3-K-ii

O

C23H30D3NO3Si MW: 402.62 73.1

50

300

275.1

285.1 332.2


100

100

150

Morphine-d6, t-butyldimethylsilyl derivative

200

(H3C)3C(H3C)2Si–O O

C23H27D6NO3Si MW: 405.63

50

250

HO

D

350

400

450

348.2

II-3-K-iii

-

405.3

N CD 3

229.1

168.1

73.1

DD

300

278.1

128.1

335.2

0 50

Relative Int. (%)

100

100

150

200

250 m/z

73.1 (H3C)3C(H3C)2Si– O

350

400

413.2

-

N CH 3

(H3C)3C(H3C)2Si–O

456.3 281.1

207.0

146.0

450

Morphine, di-t-butyldimethylsilyl derivative

II-3-L-i

O

50

300

335.1

C29H47NO3Si2 MW: 513.86

238.1

513.4


100

100

150

200

250

300

73.1 (H3C)3C(H3C)2Si– O

400

450

II-3-L-ii

O

50

350

-

281.1

207.0

459.3 335.1

149.1

550

Morphine-d3, di-t-butyldimethylsilyl derivative

414.2

N CD 3

(H3C)3C(H3C)2Si–O

500

241.2

C29H44D3NO3Si2 MW: 516.88 516.4


100

100 73.1

150

200

(H3C)3C(H3C)2Si– O

DD

O

50

250

300

350

400

II-3-L-iii

D

-

207.0

149.1

415.2 463.3

N CD 3

(H3C)3C(H3C)2Si–O

450

281.1

500

550

Morphine-d6, di-t-butyldimethylsilyl derivative C29H41D6NO3Si2 MW: 519.90

337.1

242.2

519.3

0 50

100

150

200

250

300 m/z



350

400

450

500

550

144


100

Morphine, ethyl/acetyl derivative C21H25NO4 MW: 355.43

50

O

162.1

296.2

-

N CH 3

H 3C–COO

71.2

355.2

II-3-M-i

H 5 C 2 –O

204.1

214.1

243.2

326.1

0 50

100

Relative Int. (%)

100

150

Morphine-d3, ethyl/acetyl derivative

81.1

250

400

299.2

-

N CD 3

H 3C–COO

165.1

350

II-3-M-ii

O

127.1

300

358.2

H 5 C 2 –O

C21H22D3NO4 MW: 358.45

50

200

207.1

217.1

246.2

329.2

0 50

100

Relative Int. (%)

100

150

Morphine-d6, ethyl/acetyl derivative

H 5 C 2 –O

81.2

DD

O

C21H19D6NO4 MW: 361.46

50

200

H 3C–COO

128.1

250 D

300

350 361.3

302.3

II-3-M-iii

400

-

N CD 3

210.1

220.2

249.2 332.3

168.1

0 50

100

150

200

250

300

350

400


100

Morphine, ethyl/trimethylsilyl derivative

50

73.1

C22H31NO3Si MW: 385.57

O

192.1 234.1 243.1

146.1

385.2

H 5 C 2 –O

II-3-N-i

(H3C)3Si–O

-

N CH 3

357.2 328.1

280.1

0 50

100

Relative Int. (%)

100

150

Morphine-d3, ethyl/trimethylsilyl derivative

50

73.1

C22H28D3NO3Si MW: 388.59

200

250

300

350

O

195.1 237.1 246.1

(H3C)3Si–O

450

388.2

H 5 C 2 –O

II-3-N-ii 149.1

400

-

N CD 3

360.2 327.1

283.1

0 50

100

Relative Int. (%)

100

150

Morphine-d6, ethyl/trimethylsilyl derivative 73.1

50

C22H25D6NO3Si MW: 391.61

200

250

300

II-3-N-iii

195.1

350

H 5 C 2 –O

240.2

(H3C)3Si–O

249.2 286.2

450

391.3 DD

O

149.1

400

D

-

N CD 3

360.2 329.1

0 50

100

150

200

250 m/z



300

350

400

450

145


100

50

73.1

206.1

146.1

C23H33NO3Si MW: 399.60

II-3-O-i

H 7 C 3 –O

Morphine, propyl/trimethylsilyl derivative 196.1

O

234.1

-

N CH 3

(H3C)3Si–O

257.1

399.2

371.2 356.2

280.1

0 50

100

Relative Int. (%)

100

150

200

73.1

C23H30D3NO3Si MW: 402.62

300

350

400

O

209.2 149.1

199.2

(H3C)3Si–O

237.2 260.2

450 402.3

II-3-O-ii

H 7 C 3 –O

Morphine-d3, propyl/trimethylsilyl derivative

50

250

-

N CD 3

374.2 359.2

283.1

0 50

100

Relative Int. (%)

100

150

200

Morphine-d6, propyl/trimethylsilyl derivative

50 73.1

C23H27D6NO3Si MW: 405.63

250

300

350

H 7 C 3 –O

209.2 149.1

O

240.2

200.2

(H3C)3Si–O

263.2

400

II-3-O-iii DD

450 405.3

D

-

N CD 3

374.2

286.2

362.2

300

350

0 50

Relative Int. (%)

100

100

73.1

150

200

H 7 C 3 –O

(H3C)3C(H3C)2SiO

400

341.3

II-3-P-i

O

50

250 m/z

-

299.2

271.2

N CH 3

384.3

238.2 310.2

94.2

Morphine, propyl/ t-butyldimethylsilyl derivative C26H39NO3Si MW: 441.68 398.2 441.2

206.2

146.2

450


100

100

150

200

H 7 C 3 –O

300

350

II-3-P-ii

O

50

250

341.3

73.1

(H3C)3C(H3C)2SiO

-

N CD 3

209.3

149.1

241.2

299.1

271.2

400

C26H36D3NO3Si MW: 444.70 401.3 444.5

313.3

97.1

450

Morphine-d3, propyl/ t-butyldimethylsilyl 387.4 derivative


100

100

150 H 7 C 3 –O

73.1

DD

O (H3C)3C(H3C)2SiO

50

200

250

300

350

400

343.3 D

-

II-3-P-iii

301.2

N CD 3

390.3

273.1

149.1

209.2

Morphine-d6, propyl/ t-butyldimethylsilyl derivative C26H33D6NO3Si MW: 447.71 404.3 447.4

315.3

242.0

450

97.2

0 50

100

150

200

250 m/z



300

350

400

450

146


100

Morphine, butyl/trimethylsilyl derivative

50

C24H35NO3Si MW: 413.63

73.1

II-3-Q-i 220.1 196.1

146.1

413.2

H 9 C 4 –O O

234.1

-

N CH 3

(H3C)3Si–O

356.2

271.1

385.2

324.2

0 50

100

Relative Int. (%)

100

150

200

Morphine-d3, butyl/trimethylsilyl derivative

50

300

223.2 149.1

350

400

199.1

O

237.2

450 416.3

H 9 C 4 –O

II-3-Q-ii

C24H32D3NO3Si MW: 416.64

73.1

250

-

N CD 3

(H3C)3Si–O

388.2

274.2

359.2 327.2

0 50

100

Relative Int. (%)

100

150

200

Morphine-d6, butyl/trimethylsilyl derivative

50

II-3-Q-iii

300

350

H 9 C 4 –O

223.2 240.2

450

D

-

N CD 3

(H3C)3Si–O

200.2

400 419.3

DD

O

149.1

C24H29D6NO3Si MW: 419.66

73.1

250

388.2 362.2

277.2

0 50

100

Relative Int. (%)

100

150

200

H 9 C 4 –O

73.1

50

-

300

350

355.3 398.4

299.2

II-3-R-i

O

(H3C)3C(H3C)2Si–O

250 m/z

146.1

208.1

271.2 238.2

178.2

C27H41NO3Si MW: 455.70 455.5 427.5

327.2

107.1

450

Morphine, butyl/ t-butyldimethylsilyl derivative

220.1

N CH 3

400


100

100 73.1

150

200

H 9 C 4 –O

II-3-R-ii

O

50

(H3C)3C(H3C)2Si–O

115.0

250

-

N CD 3

223.0

149.0 179.2 211.0

300

271.2

350

400 355.2

299.2

401.3

450

500

Morphine-d3, butyl/ t-butyldimethylsilyl derivative C27H38D3NO3Si MW: 458.72 458.3 430.1

241.2 327.3 344.3

0 50

100

150

200

250

300

350

400

Relative Int. (%)

100 H 9 C 4 –O

73.1

50

DD

O

(H3C)3C(H3C)2Si–O

II-3-R-iii

D

-

N CD 3

404.3

223.2

273.2

357.3

301.2

207.1

242.2

329.3

500

Morphine-d6, butyl/ t-butyldimethylsilyl derivative C27H35D6NO3Si MW: 461.74

149.2

116.1

450

348.3

432.5

461.5

0 50

100

150

200

250

300 m/z



350

400

450

500

147


100

Morphine, acetyl/trimethylsilyl derivative

50 73.1

124.1

340.2

O

C22H29NO4Si MW: 399.56

-

N CH 3

(H3C)3SiO

287.2

204.1

162.1

399.2

II-3-S-i

H 3C–COO

324.2

0 50

100

Relative Int. (%)

100

150

200

127.1

400

450 402.3

343.2

-

N CD 3

(H3C)3SiO

290.2

207.1

165.1

350

II-3-S-ii

O

C22H26D3NO4Si MW: 402.57

73.1

300

H 3C–COO

Morphine-d3, acetyl/trimethylsilyl derivative

50

250

327.2

0 50

100

Relative Int. (%)

100

73.2

150

200

Morphine-d6, acetyl/trimethylsilyl derivative

H 3C–COO

350

II-3-S-iii

D

400

450 405.4

346.3

-

N CD 3

(H3C)3SiO

128.1

300

DD

O

C22H23D6NO4Si MW: 405.59

50

250

293.2

210.2

168.1

330.4

0 50

100

Relative Int. (%)

100

150

200

250 m/z

342.2

O

204.1

162.1

450

441.3

-

267.1

229.1

400

II-3-T-i

N CH 3

(H3C)3C(H3C)2SiO

C25H35NO4Si MW: 441.64

73.1

350

H 3C–COO

Morphine, acetyl/ t-butyldimethylsilyl derivative

50

300

384.2

324.2

0 50

100

Relative Int. (%)

100

150

200

250

Morphine-d3, acetyl/ t-butyldimethylsilyl derivative

50

350 345.2

H 3C–COO O

C25H32D3NO4Si MW: 444.65

73.1

300

207.1

165.1

-

267.1

229.1

II-3-T-ii

N CD 3

(H3C)3C(H3C)2SiO

400

450

444.3

387.2

327.2


100

100 73.1

200

250

Morphine-d6, acetyl/ t-butyldimethylsilyl derivative 117.0

50

150

C25H29D6NO4Si MW: 447.67

300

H 3C–COO

348.2 DD

O

210.2

229.1

400

450

II-3-T-iii

D

-

N CD 3

(H3C)3C(H3C)2SiO

168.1

350

447.4 390.3

267.1

330.2

0 50

100

150

200

250 m/z



300

350

400

450

148


100 73.1

Morphine, propionyl/trimethylsilyl 164.1 derivative

H 5C 2–COO

196.2

C23H31SiNO4 MW: 413.58 94.1

50

O

234.2

(H3C)3Si–O

215.1

357.3

267.2

II-3-U-i

413.3

-

N CH 3

329.2 398.3

0 50

100

Relative Int. (%)

100 73.1

50

150

Morphine-d3, propionyl/trimethylsilyl derivative

200

250

300

350 360.3

H 5C 2–COO

167.1 199.2

C23H28D3SiNO4 MW: 416.60 97.1

O

237.2

(H3C)3Si–O

218.2

270.2

400

II-3-U-ii

450 416.3

-

N CD 3

332.2 401.3

0 50

100

Relative Int. (%)

100 73.1

150

Morphine-d6, propionyl/trimethylsilyl derivative

250

300 H 5C 2–COO

167.1

O

240.2 200.1

C23H25D6SiNO4 MW: 419.62

50

200

(H3C)3Si–O

221.2

273.2

350 DD

363.3 D

400

II-3-U-iii

450 419.3

-

N CD 3

332.2 404.3

97.1

0 50

100

150

200

250 m/z



300

350

400

450

149

Figure II-4. Mass spectra of hydromorphone and its deuterated analogs (hydromorphone-d3, -d6): (A) acetylderivatized; (B) [acetyl]2-derivatized; (C) [TFA]2-derivatized; (D) propionyl-derivatized; (E) PFP-derivatized; (F) [PFP]2-derivatized; (G) HFB-derivatized (H) [HFB]2-derivatized; (I) TMS-derivatized; (J) [TMS]2-derivatized; (K) tBDMS-derivatized; (L) [t-BDMS]2-derivatized; (M) MA/ethyl-derivatized; (N) MA/acetyl-derivatized; (O) MA/ propionyl-derivatized; (P) MA/TMS-derivatized; (Q) MA/t-BDMS-derivatized; (R) HA/[TMS]2-derivatized. Relative Int.(%)

100

Hydromorphone (CAS NO. 466-99-9), acetyl derivative

O

II-4-A-i

-

N CH 3

C19H21NO4 MW: 327.37

50

285.1

H 3C–COO

O

115.1

96.1

59.1

229.1

327.1

214.1

171.0

256.1


100

100

150

Hydromorphone-d3, acetyl derivative

250

288.1

O

350

II-4-A-ii

-

N CD 3 O

99.1

62.1

300

H 3C–COO

C19H18D3NO4 MW: 330.39

50

200

330.2

232.1 217.1

171.1

115.1

259.1


100

100

150 H 3C–COO

Hydromorphone-d6, acetyl derivative

65.1

250

300 291.2

DD

350

II-4-A-iii

D

O

C19H15D6NO4 MW: 333.41

50

200

-

N CD 3 O

99.1 115.0

333.2

235.1 220.1

171.1

262.2

0 50

relative Int. (%)

100

100

150

Hydromorphone, di-acetyl derivative

300

327.1

350

II-4-B-i

284.1

O

-

N CH 3

159.1 55.1

250

H 3C–COO

C21H23NO5 MW: 369.41

50

200 m/z

369.1

H 3C–COO

228.1

98.1 115.1

268.1

312.1


100

100

150

Hydromorphone-d3, di-acetyl derivative C21H20D3NO5 MW: 372.43

50

55.1

200

250

300

330.1

H 3C–COO

400

II-4-B-ii

287.1

O

159.1

350

-

N CD 3

372.2

H 3C–COO

271.1

228.1

98.1 115.1

312.1


100

100

150

Hydromorphone-d6, di-acetyl derivative

H 3C–COO

55.1

300

350 333.2

DD

D

-

N CD 3

II-4-B-iii 375.2

274.2

228.1

116.1

400

290.1

H 3C–COO

168.1 98.1

250

O

C21H17D6NO5 MW: 375.45

50

200

315.1

0 50

100

150

200

250 m/z



300

350

400

150

Figure II-4. (Continued)

Relative Int. (%)

100

Hydromorphone, di-trifluoroacetyl derivative

50 69.1

F 3C–COO

O

-

N CH 3

C21H17F6NO5 MW: 477.35

477.1

II-4-C-i

F 3C–COO

380.1 258.1 322.1

115.1

364.1 462.1

420.0

0 50

100

Relative Int. (%)

100

150

200

Hydromorphone-d3, di-trifluoroacetyl derivative

F 3C–COO

C21H14D3F6NO5 MW: 480.37

50 69.1

250

300

350

400

450 480.1

II-4-C-ii

O

500

-

N CD 3

383.1 261.1

F 3C–COO

367.1 325.1

115.1

420.0

465.1

0 50

100

relative Int. (%)

100

150

200

Hydromorphone-d6, di-trifluoroacetyl derivative

F 3C–COO

C21H11D6F6NO5 MW: 483.39

50 69.1

250 DD

O

300

350

50

100

150

500 483.1

386.1

-

N CD 3 F 3C–COO

264.1

200

450

II-4-C-iii

D

370.1 328.1

115.1

0

400

250

300

468.1

420.1

350

400

450

500


100

Hydromorphone, propionyl derivative

H 5C 2–COO O

C20H23NO4 MW: 341.40

50

-

N CH 3 O

57.1

285.1

II-4-D-i

341.1

229.1 214.1

96.1

256.1

0 50

100

Relative Int. (%)

100

Hydromorphone-d3, propionyl derivative

150 H 5C 2–COO

250

350

-

N CD 3 O

344.1

232.1

99.1

57.1

300 288.1

II-4-D-ii

O

C20H20D3NO4 MW: 344.41

50

200

217.1

259.1

0 50

100

Relative Int. (%)

100

Hydromorphone-d6, propionyl derivative

150 H 5C 2–COO O

C20H17D6NO4 MW: 347.43

50

200 DD

250

350

291.1

II-4-D-iii D

-

N CD 3 O

57.1

300

262.1

220.1

99.1

347.2

235.1

0 50

100

150

200 m/z



250

300

350

151


relative Int. (%)

100

Hydromorphone, pentafluoropropionyl derivative

II-4-E-i

50 96.1

119.0

57.1

F 5 C 2 –COO

431.1 375.1

O

-

N CH 3

C20H18F5NO4 MW: 431.35

O

284.1

402.1

346.1

0 50

100

150

Relative Int. (%)

100

250

Hydromorphone-d3, pentafluoropropionyl derivative

II-4-E-ii 50

200

300

400

F 5 C 2 –COO

450 434.1

378.1

O

-

N CD 3

C20H15D3F5NO4 119.0 MW: 434.37

99.1

350

O

60.1

287.1

405.1

349.1


100

100

150

200

250

Hydromorphone-d6, pentafluoropropionyl derivative

II-4-E-iii

300

F 5 C 2 –COO

400

450 437.1

DD

O

D

381.1

-

N CD 3

C20H12D6F5NO4 119.0 MW: 437.38

50

350

O

99.1

290.1

207.0

408.2

352.1

0 50

Relative Int. (%)

100

100

150

250 m/z

300

Hydromorphone, di-pentafluoropropionyl derivative

II-4-F-i

50

200

119.0

350

400

450

577.1

F 5 C 2 –COO

430.1

C23H17F10NO5 MW: 577.37

308.1

414.1

O

372.1

69.1

-

N CH 3 F 5 C 2 –COO

520.0


100

100

150

250

300

350

119.0

400

450

500

550

600

580.1

Hydromorphone-d3, di-pentafluoropropionyl derivative

II-4-F-ii

50

200

F 5 C 2 –COO

433.1

C23H14D3F10NO5 MW: 580.38

311.1

417.1

O

375.1

69.1

-

N CD 3 F 5 C 2 –COO

520.0


100

100

150

II-4-F-iii

50

200

250

300

350

450

500

550

600

583.1

Hydromorphone-d6, di-pentafluoropropionyl derivative

119.0

400

436.1

F 5 C 2 –COO O

C23H11D6F10NO5 MW: 583.40

314.1

420.1

D

-


378.1

69.0

DD

520.1

0 50

100

150

200

250

300

350 m/z



400

450

500

550

600

152


Relative Int. (%)

100

Hydromorphone, heptafluorobutyryl derivative

II-4-G-i 50 69.0

115.1

425.1

O

-

N CH 3

C21H18F7NO4 169.0 MW: 481.36

96.1

481.1

F 7 C 3 –COO

O

396.1

284.1

452.1

242.1

0 50

100

150

200

Relative Int. (%)

100

99.1

69.0

300

Hydromorphone-d3, heptafluorobutyryl derivative

II-4-G-ii 50

250

115.1

400

450

500 484.1

F 7 C 3 –COO

428.1

O

-

N CD 3

C21H15D3F7NO4 MW: 484.38

169.0

350

O

287.1

455.1

399.1

245.1

0 50

100

150

200

Relative Int. (%)

100

69.0

300

Hydromorphone-d6, heptafluorobutyryl derivative

II-4-G-iii 50

250

350

450

500 487.2

F 7 C 3 –COO

DD

O

431.1

D

-

N CD 3

C21H12D6F7NO4 169.0 MW: 487.40

100.1 115.1

400

290.1

O

458.1

402.1

248.2

0 50

100

150

200

250

300

350

400

450

500


100

Hydromorphone, di-heptafluorobutyryl derivative

II-4-H-i 169.0

69.0

50 207.0

480.1 358.1

C25H17F14NO5 MW: 677.38

100.0

677.1

F 7 C 3 –COO

464.1

O

422.1

F 7 C 3 –COO

-

N CH 3

266.0

658.0

0 50

100

150

200

250

Relative Int. (%)

100

350

Hydromorphone-d3, di-heptafluorobutyryl derivative

II-4-H-ii 169.0

69.0

300

50

400

207.0

500

550

600

650

361.1

700

680.1

483.1

C25H14D3F14NO5 MW: 680.40 100.0

450

F 7 C 3 –COO

467.1

O

-

N CD 3

425.1

F 7 C 3 –COO

661.2

269.1

0 50

100

150

200

250

Relative Int. (%)

100

II-4-H-iii 169.0

69.0

50

300

350

400

Hydromorphone-d6, di-heptafluorobutyryl derivative

100.1

500

600

650

700

683.1 F 7 C 3 –COO

470.1

DD

O

D

-


428.1

207.0

550

486.1 364.1

C25H11D6F14NO5 MW: 683.42

450

664.1

272.2

0 50

100

150

200

250

300

350

400 m/z



450

500

550

600

650

700

153


Relative Int. (%)

100

Hydromorphone, trimethylsilyl derivative

(H3C)3Si–O O

C20H27NO3Si MW: 357.52

50

300.1

-

N CH 3 O

73.1 96.1

357.2

II-4-I-i 342.1

255.1

243.1

314.1

216.1

0 50

100

Relative Int. (%)

100

150

Hydromorphone-d3, trimethylsilyl derivative

50

200

300

350

(H3C)3Si–O

-

N CD 3 O

99.1

400 360.2

II-4-I-ii

O

C20H24D3NO3Si MW: 360.54

73.1

250

300.1

243.1

255.1

216.1

345.2 317.2

0 50

100

Relative Int. (%)

100

150

Hydromorphone-d6, trimethylsilyl derivative

200 (H3C)3Si–O

C20H21D6NO3Si MW: 363.56

50

O

250 DD

300

D

-

301.1

O

217.1

100.1

400 363.2

II-4-I-iii

N CD 3

73.1

350

255.1

243.1

348.2 320.2

0 50

100

150

200

250

300

350

400


100

Hydromorphone, 73.1 di-trimethylsilyl derivative

50

O

234.1

C23H35NO3Si2 MW: 429.70

414.2

II-4-J-i

(H3C)3Si–O

429.2

-

N CH 3

357.1 371.1

(H3C)3Si–O

184.1

324.1

272.1


100

100

150

200

Hydromorphone-d3, 73.1 di-trimethylsilyl derivative

50

C23H32D3NO3Si2 MW: 432.72

250

300

350

417.2

O

-

N CD 3 (H3C)3Si–O

187.1

450 432.2

II-4-J-ii

(H3C)3Si–O

237.1

400

327.1

275.1

357.1 371.1


100

100

150

200

250

Hydromorphone-d6, 73.1 di-trimethylsilyl derivative

50

C23H29D6NO3Si2 MW: 435.74

300 (H3C)3Si–O O

240.2

350 DD

400

450 435.2

II-4-J-iii

417.2

D

-

N CD 3

(H3C)3Si–O

188.1

330.2 275.1

357.1

373.2

0 50

100

150

200

250 m/z



300

350

400

450

154


Relative Int. (%)

100

299.1


II-4-K-i

Hydromorphone, t-butyldimethylsilyl derivative

-

N CH 3

50

C23H33NO3Si MW: 399.60

342.2

O

229.1

73.1

257.1

399.2

0 50

100

150

200

250

300

Relative Int. (%)

100

350

299.1


400

II-4-K-ii

-

N CD 3

50

345.2

O

229.1

73.1

450

Hydromorphone-d3, t-butyldimethylsilyl derivative C23H30D3NO3Si MW: 402.62

257.1

402.2

0 50

100

150

200

250

300

Relative Int. (%)

100

350 301.1

(H3C)3C(H3C)2Si–O

DD

O

400

II-4-K-iii

D

-

50

N CD 3

348.2

O

73.1

231.1

450

Hydromorphone-d6, t-butyldimethylsilyl derivative C23H27D6NO3Si MW: 405.63

259.1

405.3

0 50

100

Relative Int. (%)

100

150

200

Hydromorphone, di-t-butyldimethylsilyl derivative 73.1

50

250 m/z

300

(H3C)3C(H3C)2Si–O

350

II-4-L-i

O

-

N CH 3

C29H47NO3Si2 MW: 513.86

400

450

456.2

413.2

(H3C)3C(H3C)2Si–O

207.1

513.3

498.3

0 50

100

Relative Int. (%)

100

150

200

250

Hydromorphone-d3, di-t-butyldimethylsilyl derivative

73.1

50

300

350

400

(H3C)3C(H3C)2Si–O

II-4-L-ii

O

-

N CD 3

C29H44D3NO3Si2 MW: 516.88

450

100

Relative Int. (%)

73.1

150

200

501.3

250

Hydromorphone-d6, di-t-butyldimethylsilyl derivative

300

350

(H3C)3C(H3C)2Si–O

DD

O

400 D

450

II-4-L-iii

-

N CD 3

C29H41D6NO3Si2 MW: 519.90

50

150

462.3

504.3

200

250

300 m/z

350



550

415.2

207.0

100

500

516.3

(H3C)3C(H3C)2Si–O

0 50

459.3

413.2

207.1

50

550

(H3C)3C(H3C)2Si–O

0 100

500

400

450

500

519.3

550

155


Relative Int. (%)

100

Hydromorphone, methoxyimino/ethyl derivative

H 5 C 2 –O O

C20H26N2O3 MW: 342.43

50 70.1

311.2

II-4-M-i

342.2

-

N CH 3 H 3CO–N

123.1

82.1 115.1

284.1

171.1

327.2

254.1

199.1

0 50

100

Relative Int. (%)

100

150

200

Hydromorphone-d3, methoxyimino/ethyl derivative

73.1

300

350 345.3

H 5 C 2 –O

314.2

II-4-M-ii

O

-

N CD 3

C20H23D3N2O3 MW: 345.45

50

250

H 3CO–N

126.1

85.1 115.0

285.2

171.1

330.2

254.1

199.0


100

100

150

200

Hydromorphone-d6, methoxyimino/ethyl derivative

H 5 C 2 –O

86.2

300

350 348.3

317.3 DD

II-4-M-iii

D

O

-

N CD 3

C20H20D6N2O3 MW: 348.47

50

250

H 3CO–N

115.1

127.1 171.1

199.1

254.1

285.1

333.2

0 50

100

Relative Int. (%)

100

150

200 m/z

Hydromorphone, methoxyimino/acetyl derivative

50 82.1

115.1

250

H 3C–COO

300

283.3

O

314.2

II-4-N-i

-

N CH 3

C20H24N2O4 123.1 MW: 356.42

350

356.3

257.1

H 3CO–N

325.3

0 50

100

Relative Int. (%)

100

150

200

Hydromorphone-d3, methoxyimino/acetyl derivative

50

115.2 85.1

250

300

H 3C–COO

286.3

O

350 317.3

II-4-N-ii

-

N CD 3

C20H21D3N2O4 126.1 MW: 359.43

359.3

257.2

H 3CO–N

400

328.2

0 50

100

Relative Int. (%)

100

150

200

Hydromorphone-d6, methoxyimino/acetyl derivative

50 86.2 115.2

250

300

350 320.3

H 3C–COO

DD

O

II-4-N-iii

289.3 D

-

362.3

N CD 3

127.2 C20H18D6N2O4 MW: 362.45

H 3CO–N

400

258.2

331.3

0 50

100

150

200

250 m/z



300

350

400

156


Relative Int. (%)

100

Hydromorphone, methoxyimino/propionyl derivative

50

283.1

O

-

N CH 3

C21H26N2O4 MW: 370.44 57.1

314.2

H 5C 2–COO

II-4-O-i

H 3CO–N

123.1

82.1

370.3

257.1

339.2

0 50

100

Relative Int. (%)

100

150

85.1

300

350

400

H 5C 2–COO

II-4-O-ii

O

286.2

-

N CD 3

C21H23D3N2O4 MW: 373.46 57.1

250

317.2

Hydromorphone-d3, methoxyimino/propionyl derivative

50

200

H 3CO–N

373.2

257.1

342.3

126.1

0 50

100

Relative Int. (%)

100

150

Hydromorphone-d6, methoxyimino/propionyl derivative

50

200

II-4-O-iii

86.1

300

350

400

320.2

H 5C 2–COO

DD

D

O

C21H20D6N2O4 MW: 376.48 57.1

250

289.2

-

N CD 3

376.3

H 3CO–N

127.1

257.2

345.2

0 50

100

150

200

250

300

350

400


100

Hydromorphone, methoxyimino/ trimethylsilyl derivative 73.1

50

82.1

II-4-P-i

(H3C)3Si–O

355.2

O

H 3CO–N

153.1

207.0

371.2

-

N CH 3

C21H30N2O3Si MW: 386.56 123.1

314.1 340.2

243.1

216.1

386.3

0 50

100

Relative Int. (%)

100 73.1

50

150

200

Hydromorphone-d3, methoxyimino/ trimethylsilyl derivative C21H27D3N2O3Si MW: 389.58 126.1 85.1

II-4-P-ii

250

300

350 389.3

(H3C)3Si–O

358.3

O

-

374.3

N CD 3 H 3CO–N

156.1

207.1

216.1

400

314.2 343.2

243.1

0 50

100

Relative Int. (%)

100

150

Hydromorphone-d6, methoxyimino/ trimethylsilyl derivative 73.1

50

200

II-4-P-iii

250 (H3C)3Si–O O

300 DD

350 361.3

-

H 3CO–N

218.1

392.3

D

377.3

N CD 3

C21H24D6N2O3Si MW: 392.60 127.1 86.1

400

314.1 345.2

243.1

0 50

100

150

200

250 m/z



300

350

400

157


Relative Int. (%)

100

299.1

(H3C)3C(H3C)2Si–O Hydromorphone, methoxyimino/ O t-butyldimethylsilyl derivative

50

C24H36N2O3Si 73.1 MW: 428.64

-

N CH 3

342.2

H 3CO–N

216.1

229.1

203.1

II-4-Q-i

257.1

371.2

328.2

399.3

428.3

0 50

100

Relative Int. (%)

100

150

200

250

300

350

400

(H3C)3C(H3C)2Si–O

Hydromorphone-d3, methoxyimino/ t-butyldimethylsilyl derivative

50

73.1 C24H33D3N2O3Si MW: 431.66 126.1

374.2

O

450

II-4-Q-ii

-

N CD 3 H 3CO–N

203.1

275.2

216.1 229.1 255.1

299.1

328.2

431.4

343.2

400.3

0 50

100

Relative Int. (%)

100

150

200

250

300

73.1 C24H30D6N2O3Si MW: 434.68 127.1

DD

450

II-4-Q-iii

D

-

N CD 3

H 3CO–N

203.1

400 377.3

(H3C)3C(H3C)2Si–O Hydromorphone-d6, methoxyimino/ O t-butyldimethylsilyl derivative

50

350

434.4

330.2

278.2

299.1

346.2

218.1 231.1 257.1

403.3

0 50

Relative Int. (%)

100

100

73.1

150

Hydromorphone, hydroxylimino/ di-trimethylsilyl derivative C23H36N2O3Si2 MW: 444.71 123.1

50

200

250 m/z

300

350

(H3C)3Si–O

450

II-4-R-i

355.2

444.3

O

-

N CH 3

429.3

(H3C)3Si–O–N

216.1

400

372.2

339.1

243.1


100

100 73.1

150

200

Hydromorphone-d3, hydroxylimino/ di-trimethylsilyl derivative

126.1

300

350

400

(H3C)3Si–O

500

II-4-R-ii 447.3

-

432.3

(H3C)3Si–O–N

216.0

450

358.2

O

N CD 3

C23H33D3N2O3Si2 MW: 447.73

50

250

342.2

243.1

372.2


100

100 73.1

150

200

Hydromorphone-d6, hydroxylimino/ di-trimethylsilyl derivative

250

300

(H3C)3Si–O

DD

O

C23H30D6N2O3Si2 MW: 450.75

50

350

400

361.3

450.3

-

N CD 3

243.1

500

II-4-R-iii D

435.3

(H3C)3Si–O–N

127.2

450

345.2

373.1

0 50

100

150

200

250

300 m/z



350

400

450

500

158

Figure II-5. Mass spectra of oxymorphone and its deuterated analogs (oxymorphone-d3): (A) [acetyl]2-derivatized; (B) [acetyl]3-derivatized; (C) [TFA]2-derivatized; (D) propionyl-derivatized; (E) [propionyl]2-derivatized; (F) [propionyl]3derivatized; (G) [PFP]2-derivatized; (H) [HFB]2-derivatized; (I) [TMS]2-derivatized; (J) [TMS]3-derivatized; (K) t-BDMSderivatized; (L) MA/ethyl-derivatized; (M) MA/acetyl-derivatized; (N) MA/[acetyl]2-derivatized; (O) MA/propionyl-derivatized; (P) MA/[HFB]2-derivatized; (Q) MA/[TMS]2-derivatized; (R) MA/[t-BDMS]2-derivatized; (S) MA/ethyl/propionyl-derivatized; (T) MA/ethyl/TMS-derivatized; (U) MA/ethyl/t-BDMS-derivatized; (V) MA/acetyl/TMS-derivatized; (W) MA/propionyl/ TMS; (X) HA/[TMS]3-derivatized; (Y) HA/[ethyl]2/propionyl-derivatized; (Z) HA/[ethyl]2/TMS-derivatized. Relative Int. (%)

100

Oxymorphone (CAS NO. 76-41-5), di-acetyl derivative

OOC–CH 3

O

C21H23NO6 MW: 385.41

50

343.1

H 3C–COO

-

N CH 3

II-5-A-i 300.1 385.1

O

203.1

115.1

284.1

226.1

0 50

100

Relative Int. (%)

100

150

200

250

50

206.1

115.1

100

II-5-A-ii

-

303.1

229 .1

200

388.2

287.1

250

300

350

400

m/z


150

400

N CD 3

O

0 50

OOC–CH 3

O

C21H20D3NO6 MW: 388.43

350 346.2

H 3C–COO

Oxymorphone-d3 (CAS NO. 142225-03-2), di-acetyl derivative

300

Oxymorphone, tri-acetyl derivative

H 3C–COO O

C23H25NO7 MW: 427.45

50

385.1

OOC–CH 3

II-5-B-i

-

N CH 3

427.2

H 3C–COO

342.1

226.1

282.1 326.1

0 Relative Int. (%)

100

50

100

150

200

250

Oxymorphone-d3, tri-acetyl derivative

300 OOC–CH 3

O

50

400

450

388.2

H 3C–COO

C23H22D3NO7 MW: 430.47

350

II-5-B-ii

-

430.2

N CD 3

H 3C–COO

285.1

226.1

345.1 329.1

0 50

100

Relative Int. (%)

100

150

200

250 m/z

Oxymorphone, di-trifluoroacetyl derivative

F 3C–COO

70.1

350

II-5-C-i

-

N CH 3

261.1

208.1

450 493.1

O

115.1

400

OOC–CF 3

O

C21H17F6NO6 MW: 493.35

50

300

396.1

368.1

312.1

474.1

0 50

100

Relative Int. (%)

100

150

200

250

Oxymorphone-d3, di-trifluoroacetyl derivative

50 73.1

300 F 3C–COO O

C21H14D3F6NO6 MW: 496.37

350

400

162.1

115.1

500 496.1

OOC–CF 3

II-5-C-ii

-

N CD 3

O

264.0

450

399.1 371.1

315.1

477.1

0 50


100

150

200

250


350

400

450

500

159


Relative Int. (%)

100

Oxymorphone, propionyl derivative

II-5-D-i

OH

O

C20H23NO5 MW: 357.40

50

301.1

H 5C 2–COO

-

N CH 3

O

57.1

203.1

115.1

357.1

216.1

244.1

272.1

0 50

100

relative Int. (%)

100

150

200

Oxymorphone-d3, propionyl derivative

H 5C 2–COO

300

350

400

304.1

OH

O

C20H20D3NO5 MW: 360.42

50

250

II-5-D-ii

-

N CD 3

O

57.1

206.1

115.1

360.1

219.1

244.0

275.1

0 50

100

150

200

250

300

350

400


100

Oxymorphone, di-propionyl derivative

50

OOC–C 2H 5

O

C23H27NO6 MW: 413.46

-

N CH 3

O

57.1

II-5-E-i

357.1

H 5C 2–COO

300.1 284.1

203.1

413.1 340.1

0 50

100

Relative Int. (%)

100

150

200

Oxymorphone-d3, di-propionyl derivative

250

400

450

II-5-E-ii

OOC–C 2H 5

O

-

N CD 3

303.1

O

57.1

350 360.1

H 5C 2–COO

C23H24D3NO6 MW: 416.48

50

300

287.1

206.1

416.2 343.1

0 50

100

Relative Int. (%)

100

150

200

Oxymorphone, tri-propionyl derivative

250 m/z

57.1

216.1 226.1

400

450

II-5-F-i

OOC–C 2H 5

O

H 5C 2–COO

350

413.1

H 5C 2–COO

C26H31NO7 MW: 469.53

50

300

-

N CH 3

469.2 282.1

340.1

356.1

322.1

396.2

0 50

100

Relative Int. (%)

100

150

200

Oxymorphone-d3, tri-propionyl derivative

250

H 5C 2–COO

219.1

226.1

400

450

500

II-5-F-ii

OOC–C 2H 5

O

57.1

350

416.2

H 5C 2–COO

C26H28D3NO7 MW: 472.55

50

300

-

N CD 3

472.2 285.1

343.1 325.1

359.1

399.2

0 50

100

150

200

250

300 m/z



350

400

450

500

160


Relative Int. (%)

100

Oxymorphone, di-pentafluoropropionyl derivative

50

-

N CH 3

446.1

O

311.0

258.0

593.1

II-5-G-i

OOC–C 2 F 5

O

C23H17F10NO6 MW: 593.37

119.0

70.1

F 5 C 2 –COO

418.1

574.1

0 50

100

150

Relative Int. (%)

100

200

250

300

350

Oxymorphone-d3, di-pentafluoropropionyl derivative 119.0

50

F 5 C 2 –COO

450

314.0 261.1

500

550

600

650

600

650

596.1

II-5-G-ii

OOC–C 2 F 5

O

C23H14D3F10NO6 MW: 596.39

73.1

400

-

N CD 3

449.1

O

421.1

577.1

0 50

100

150

200

250

300

350 m/z

400

Relative Int. (%)

100 F 7 C 3 –COO

169.0

69.0

O

50 207.0

O

115.1

OOC–C 3 F 7

-

N CH 3

361.0 308.1

450

500

550

II-5-H-i

Oxymorphone, di-heptafluorobutyryl derivative

496.1

C25H17F14NO6 MW: 693.38

468.2

693.1

674.1

0 50

100

150

200

250

Relative Int. (%)

100

F 7 C 3 –COO

169.0

73.1

300

O

50

350

500

550

499.1

-

N CD 3

364.0

600

650

Oxymorphone-d3, di-heptafluorobutyryl derivative

II-5-H-ii

311.1

207.0

450

OOC–C 3 F 7

O

115.1

400

700

750

696.1

C25H14D3F14NO6 MW: 696.40 677.1

471.1

0 50

100

Relative Int. (%)

100

150

200

Oxymorphone, di-trimethylsilyl derivative

50

73.1

C23H35NO4Si2 MW: 445.70

250

300

(H3C)3Si–O O

350

400 m/z

450

500

550

600

700

750

445.2

II-5-I-i

O–Si(CH3)3

650

-

N CH 3

O

260.1

287.1

331.1

371.3

430.2

0 50

100

Relative Int. (%)

100

150

200

Oxymorphone-d3, (H C) Si–O 3 3 di-trimethylsilyl derivative O

50

73.1

C23H32D3NO4Si2 MW: 448.72

250

300

350

400

500

450

500

448.2

II-5-I-ii

O–Si(CH3)3

450

-

N CD 3

O

331.1

263.1

371.3

433.2

0 50

100

150

200

250

300 m/z



350

400

161


Relative Int. (%)

100

73.1

Oxymorphone, tri-trimethylsilyl derivative

50

(H3C)3Si–O

O–Si(CH3)3

O

C26H43NO4Si3 MW: 517.88

502.2

-

N CH 3

(H3C)3Si–O

355.1

412.2

232.1

147.1

517.3

II-5-J-i

0 50 relative Int. (%)

100

100 73.1

150

200

250

Oxymorphone-d3, tri-trimethylsilyl derivative

350

(H3C)3Si–O

400

O–Si(CH3)3

O

C26H40D3NO4Si3 MW: 520.90

50

300

450

550 520.3

II-5-J-ii

505.2

-

N CD 3

(H3C)3Si–O

355.1 415.2

242.1

147.1

500

0 50

100

150

200

250

300 m/z

350

400

450

Relative Int. (%)

100 (H3C)3C(H3C)2SiO O

50

500

358.1

II-5-K-i

OH

Oxymorphone, t-butyldimethylsilyl derivative

-

N CH 3

255.1

O

C23H33NO4Si MW: 415.60

315.1 297.1

216.0

73.1

550

330.2

415.2

0 50

100

150

200

250

300

350

Relative Int. (%)

100 (H3C)3C(H3C)2SiO O

50

400 361.2

II-5-K-ii

OH

Oxymorphone-d3, t-butyldimethylsilyl derivative

-

N CD 3

255.1

O

73.1

C23H30D3NO4Si MW: 418.62

315.1 297.1

216.1

450

333.2

418.2

0 50

Relative Int. (%)

100

100

150

200

Oxymorphone, methoxyimino/ethyl derivative

70.1

300

350

400

450

358.2

H 5 C 2 –O

OH

O

C20H26N2O4 MW: 358.43

50

250 m/z

II-5-L-i

-

N CH 3

H 3CO–N

244.1

214.1

115.1

270.1

301.2

327.2


100

100

150

Oxymorphone-d3, methoxyimino/ethyl derivative

250

300

350

400 361.2

H 5 C 2 –O

OH

O

C20H23D3N2O4 MW: 361.45

50

200

II-5-L-ii

-

N CD 3

H 3CO–N

73.1 115.0

247.1

217.1

302.2

330.1

0 50

100

150

200

250 m/z



300

350

400

162


Relative Int. (%)

100

OH

O

C20H24N2O5 MW: 372.42

50

372.2

H 3C–COO

Oxymorphone, methoxyimino/acetyl derivative

II-5-M-i

-

N CH 3

H 3CO–N

216.1

329.2

258.1

115.0

355.2

281.1


100

100

150

200

Oxymorphone-d3, methoxyimino/acetyl derivative

50

250

350

400 375.2

H 3C–COO

OH

O

C20H21D3N2O5 MW: 375.43

300

II-5-M-ii

-

N CD 3

H 3CO–N

219.1

115.2

261.1

332.2

284.2

358.2

0 50

100

150

200

250

300

350

400


100

H 3C–COO

Oxymorphone, methoxyimino/di-acetyl derivative

O

C22H26N2O6 MW: 414.45

50

372.2

OCOCH3

II-5-N-i

414.2

-

N CH 3

H 3CO–N

258.1

216.1

115.1

329.1

281.2


100

100

150

200

Oxymorphone-d3, methoxyimino/di-acetyl derivative

300

350

400

450

375.2

H 3C–COO

OCOCH3

O

C22H23D3N2O6 MW: 417.47

50

250

II-5-N-ii

417.2

-

N CD 3

H 3CO–N

218.2

115.1

261.2

332.2

284.1

0 50

100

Relative Int. (%)

100

150

200

250 m/z H 5C 2–COO

Oxymorphone, methoxyimino/propionyl derivative C21H26N2O5 MW: 386.44

50 57.1

70.1

300

O

177.2

115.0 157.1

350

400

450

330.2 OH

-

II-5-O-i

N CH 3

386.2

H 3CO–N

299.1

203.1

273.2

355.2

0 50

100

Relative Int. (%)

100

150

200

Oxymorphone-d3, methoxyimino/propionyl derivative

50 57.1 73.1

250 H 5C 2–COO O

C21H23D3N2O5 MW: 389.46

300

350

400

333.2 OH

II-5-O-ii

-

N CD 3

389.2

H 3CO–N

115.1

206.1

174.1

302.1

274.2

358.2

0 50

100

150

200

250 m/z



300

350

400

163


Relative Int .(%)

100

169.1

Oxymorphone, methoxyimino/di-heptafluorobutyryl derivative

69.1

50

II-5-P-i

F 7 C 3 CO–O

O–COC 3 F 7

O

C26H20F14N2O6 MW: 722.42

412.2

525.3

477.2 509.1

-

N CH 3

H 3CO–N

722.3

0 50

100

150

Relative Int .(%)

100

200

250

169.0

350

400

450

Oxymorphone-d3, methoxyimino/di-heptafluorobutyryl derivative

500

550

II-5-P-ii

600

650

F 7 C 3 CO–O

700

415.2

528.2

480.3 512.3

750

O–COC 3 F 7

O

C26H17D3F14N2O6 MW: 725.44

69.1

50

300

-

N CD 3

H 3CO–N

725.4

0 50

100

150

Relative Int. (%)

100

200

250

300

350

400 m/z

Oxymorphone, methoxyimino/ di-trimethylsilyl derivative 73.1

50

450

500

(H3C)3Si–O

600

650

750

474.3

-

N CH 3

H 3CO–N

459.3

287.2 312.1

260.1

700

II-5-Q-i

O–Si(CH3)3

O

C24H38N2O4Si2 MW: 474.74

550

353.2

401.2

417.2

0 50

100

Relative Int. (%)

100

150

200

250

300

Oxymorphone-d3, methoxyimino/ di-trimethylsilyl derivative 73.1

50

350

(H3C)3Si–O

450

500 477.3

II-5-Q-ii

O–Si(CH3)3

O

C24H35D3N2O4Si2 MW: 477.76

400

-

N CD 3

H 3CO–N

462.3

290.2 312.2

263.2

356.2

404.3

417.3

0 50

100

150

200

250

300

350

400

450

500


100

73.1

50

Oxymorphone, methoxyimino/dit-butyldimethylsilyl derivative

C30H50N2O4Si2 91.1 MW: 558.59

208.1

(H3C)3C(H3C)2Si–O

O–Si(CH3)2C(CH3)3

O

255.1

-

440.4

H 3CO–N

369.4

299.2 329.3

II-5-R-i 501.3

N CH 3

543.1

402.1

558.4


100

100 73.1

89.1

50

150

200

250

Oxymorphone-d3, methoxyimino/dit-butyldimethylsilyl derivative C30H47D3N2O4Si2 MW: 561.92

300

350

400


H 3CO–N

208.1

332.4

282.2

450

500

O–Si(CH3)2C(CH3)3

550

504.4

600

II-5-R-ii

-

N CD 3

390.5

443.3 546.5

561.3

0 50

100

150

200

250

300

350 m/z



400

450

500

550

600

164


Relative Int. (%)

100

H 5C 2–COO

Oxymorphone, methoxyimino/ethyl/ propiony derivative

II-5-S-i

C23H30N2O5 MW: 414.49

50

414.3

O–C 2 H 5

O

-

N CH 3

H 3CO–N

357.2

244.1

385.1

214.1

57.1

309.2

341.1

0 50

100

Relative Int. (%)

100

150

200

Oxymorphone-d3, methoxyimino/ethyl/ propiony derivative

250

II-5-S-ii

350

400

-

N CD 3

H 3CO–N

360.2 388.2

247.1

57.1

450 417.3

O–C 2 H 5

O

C23H27D3N2O5 MW: 417.51

50

300

H 5C 2–COO

312.2

217.1

344.2

0 50

100

Relative Int. (%)

100

150

200

Oxymorphone, methoxyimino/ethyl/ trimethylsilyl derivative

50

250 m/z

300

H 5 C 2 –O

II-5-T-i

214.1

100

-

415.3

243.1

Relative Int. (%)

373.2

309.1

150

200

Oxymorphone-d3, methoxyimino/ethyl/ trimethylsilyl derivative

250

300

H 5 C 2 –O

II-5-T-ii

350

401.2

400

450 433.3

O–Si(CH3)3

O

C23H31D3N2SiO4 73.1 MW: 433.63

50

430.3

N CH 3

0 50

450

H 3CO–N

115.1

100

400

O–Si(CH3)3

O

C23H34N2SiO4 73.1 MW: 430.61

350

-

N CD 3

H 3CO–N

217.1

246.2

115.1

373.2

312.2

418.3 404.3

0 50

100

150

Relative Int. (%)

100

200

H 5 C 2 –O O

50

250 m/z

300

350

358.2

II-5-U-i

O–Si(CH3)2C(CH3)3

-

N CH 3

400

Oxymorphone, methoxyimino/ethyl/ t-butyldimethylsilyl derivative C26H40N2O4Si MW: 472.69

H 3CO–N

70.1

214.1

115.1

450

301.2 327.2

244.1

0 50

100

150

Relative Int. (%)

100

200

H 5 C 2 –O O

50

250

300

350

II-5-U-ii

O–Si(CH3)2C(CH3)3

-

400 361.2

N CD 3

217.1

115.0

500

Oxymorphone-d3, methoxyimino/ethyl/ t-butyldimethylsilyl derivative C26H37D3N2O4Si MW: 475.71

H 3CO–N

73.1

450

247.1

301.2

330.1

0 50

100

150

200

250

300 m/z



350

400

450

500

165


Relative Int. (%)

100

Oxymorphone, methoxyimino/acetyl/ trimethylsilyl derivative

402.3

-

N CH 3

H 3CO–N

203.1

115.1

O–Si(CH3)3

O

215.1

73.1 C H N O Si 23 32 2 5 MW: 444.60

50

444.3

H 3C–COO

II-5-V-i

312.2

281.2

255.1

174.1

345.2

429.3

371.2

0 50

100

Relative Int. (%)

100

150

200

Oxymorphone-d3, methoxyimino/acetyl/ trimethylsilyl derivative

73.1

50

250

350

218.1

400

450 447.3

H 3C–COO

II-5-V-ii

C23H29D3N2O5Si MW: 447.62

O–Si(CH3)3

O

405.3

-

N CD 3

H 3CO–N

206.1

174.1

115.1

300

255.1

315.2

284.1

345.2

432.2

374.3

0 50

100

Relative Int. (%)

100

150

Oxymorphone, methoxyimino/propionyl/ trimethylsilyl derivative

50

C24H34N2O5Si MW: 458.63

73.1

200

250 m/z

300

II-5-W-i

H 5C 2–COO

350

400

450

458.3

402.3 O–Si(CH3)3

O

-

N CH 3

215.1 H 3CO–N

203.1

255.0

312.1

345.1

443.2

371.1

0 50

100

Relative Int. (%)

100

150

200

Oxymorphone-d3, methoxyimino/propionyl/ trimethylsilyl derivative

50

C24H31D3N2O5Si MW: 461.65

73.1

250

II-5-W-ii

300

350

400

450

500 461.3

405.2

H 5C 2–COO

O–Si(CH3)3

O

-

N CD 3

218.1 H 3CO–N

206.2

255.1

345.2

315.1

446.3

374.3

0 50

100

150

200

250

300

350

400

450

500


100

73.1

Oxymorphone, hydroxylimino/ tri-trimethylsilyl derivative

II-5-X-i

(H3C)3Si–O O

C26H44N2O4Si3 MW: 532.89

50

427.3


100

100 73.1

150

200

Oxymorphone-d3, hydroxylimino/ tri-trimethylsilyl derivative

250

300

350

II-5-X-ii

400

(H3C)3Si–O O

C26H41D3N2O4Si3 MW: 535.91

50

290.2

150

200

250

300 m/z



450

O–Si(CH3)3

517.3

500

550

535.3

-

N CD 3

430.3

0 100

459.2

(H3C)3Si–O–N

147.2

50

-

N CH 3

287.1 (H3C)3Si–O–N

147.0

532.3

O–Si(CH3)3

350

400

462.3

450

520.3

500

550

166


Relative Int. (%)

100

Oxymorphone, hydroxylimino/di-ethyl/ propionyl derivative

50

H 5C 2–COO

II-5-Y-i

O

C24H32N2O5 MW: 428.53

57.2

244.2

115.1

-

N CH 3

371.3

H 5 C 2 –O–N

214.0

173.2

428.3 O–C 2 H 5

399.4

309.3 355.2

0 50

100

Relative Int. (%)

100

150

Oxymorphone-d3, hydroxylimino/di-ethyl/ propionyl derivative

50

200

250

II-5-Y-ii

H 5C 2–COO O

C24H29D3N2O5 MW: 431.55

57.1

115.1

300

350

400

431.4 O–C 2 H 5

374.2

-

N CD 3

247.3 H C –O–N 5 2

402.3

312.2 358.3

217.1

175.1

450

0 50

100

Relative Int. (%)

100 73.1

50

150

Oxymorphone, hydroxylimino/di-ethyl/ trimethylsilyl derivative C24H36N2O4Si MW: 444.63

200

250 m/z

300

H 5 C 2 –O

II-5-Z-i

O

350

400

450

444.4

O–Si(CH3)3

-

N CH 3

H 5 C 2 –O–N

214.2

231.1

243.2

429.4 309.3

325.3 371.3

399.3

0 50

100

Relative Int. (%)

100 73.1

50

150

Oxymorphone-d3, hydroxylimino/di-ethyl/ trimethylsilyl derivative C24H33D3N2O4Si MW: 447.65

200

250

300 H 5 C 2 –O

II-5-Z-ii

O

217.3

246.1 234.3

100

150

200

250 m/z

312.3

300



400

450 447.3

O–Si(CH3)3

-

N CD 3

H 5 C 2 –O–N

0 50

350

432.3 328.2

350

374.3 402.3

400

450

167

Figure II-6. Mass spectra of 6-acetylcodeine and its deuterated analogs (6-acetylcodeine-d3).

Relative Int. (%)

100

6-Acetylcodeine (CAS NO. 6703-27-1) C20H23NO4 MW: 341.41

O

50 59.1

H3CO

115.0

81.0

H 3C–COO

124.0

II-6-i -

N CH 3

282.1 341.1

229.0

204.0

162.0

266.1

298.1

326.0


100

100

150

6-Acetylcodeine-d3

O H 3C–COO

62.1

115.0

81.0

250

H3CO

C20H20D3NO4 MW: 344.39

50

200

II-6-ii -

N CD 3

350 344.1

285.1

232.1

207.0

165.0

127.0

300

269.1

301.1

329.1

0 50

100

150

200 m/z



250

300

350

168

Figure II-7. Mass spectra of codeine and its deuterated analogs (codeine-d3, -d6, 13C1-d3): (A) underivatized; (B) acetylderivatized; (C) TFA-derivatized; (D) propionyl-derivatized; (E) PFP-derivatized; (F) HFB-derivatized; (G) TMSderivatized; (H) t-BDMS-derivatized.

Relative Int. (%)

100

Codeine (CAS NO. 76-57-3) C18H21NO3 MW: 299.36

50

299.1

H3CO O

124.1

115.1

59.1

-

N CH 3

HO

162.1

II-7-A-i

229.1 214.1

188.1

282.1


100

100

150

200

Codeine-d3 (CAS NO. 70420-71-2)

302.2

O

165.1

350

II-7-A-ii

-

N CD 3

HO

232.1

127.1

115.1

62.1

300

H3CO

C18H18D3NO3 MW: 302.38

50

250

217.1

188.1

285.2


100

100

150

200

Codeine-d6

300 305.2

D3CO

C18H15D6NO3 MW: 305.40

50

250

O

165.1 127.1

115.1

62.1

II-7-A-iii

-

N CD 3

HO

235.1 217.1

191.1

350

288.2


100

100

150

200

Codeine-13C1-d3 C17 1H18D3NO3 MW: 303.38

303.2

O

166.1 128.1

115.1

63.1

300

H3CO

13C

50

250

II-7-A-iv

13 N— CD3

HO

218.1

188.1

350

233.1 284.2

0 50

Relative Int. (%)

100

100

II-7-B-i

150

341.2

-

N CH 3

124.1

81.1

300

350

Codeine, acetyl derivative

282.1

H 3C–COO

59.1

250

H3CO O

50

200 m/z

C20H23NO4 MW: 341.40

229.1 204.1

162.1

298.1


100

100

150

300

350

-

81.1

C20H20D3NO4 MW: 344.42

N CD 3

H 3C–COO

232.1 127.1

400 Codeine-d3, acetyl derivative

344.2 285.2

O

62.1

250

H3CO

II-7-B-ii

50

200

207.1

165.1

301.2

0 50

100

150

200

250



300

350

400

169


Relative Int. (%)

100

D3CO

II-7-B-iii

347.2

O

-

127.1

81.1

C20H17D6NO4 MW: 347.44

N CD 3

H 3C–COO

50 62.1

Codeine-d6, acetyl derivative

288.2

235.1 207.1

165.1

304.2

0 50

100

150

Relative Int. (%)

100

200

300

H3CO

II-7-B-iv 50 128.1

345.2

13

N— CD3

H 3C–COO

81.1

350

286.1

O

63.1

250

400

Codeine-13C1-d3, acetyl derivative C1913C1H20D3NO4 MW: 345.41

233.1

208.1

165.1

302.1

0 50

100

150

200

250

300

350

400


100

50

282.1

Codeine, trifluoroacetyl derivative

H3CO

C20H20F3NO4 MW: 395.37

F 3C–COO

O

115.1

69.1

152.1

II-7-C-i

395.1

-

N CH 3

225.1

338.0


100

100

150

200

Codeine-d3, trifluoroacetyl derivative

50

O F 3C–COO

350

II-7-C-ii

400

450

398.1

-

N CD 3

225.1

152.0

115.0

300 285.1

H3CO

C20H17D3F3NO4 MW: 398.39 69.0

250

338.0


100

100

150

200

Codeine-d6, trifluoroacetyl derivative

50

O F 3C–COO

350

II-7-C-iii

400

450

401.1

-

N CD 3

228.1

152.0

115.0

300 288.1

D3CO

C20H14D6F3NO4 MW: 401.41 69.1

250

341.1


100

100

150

200

Codeine-13C1-d3, trifluoroacetyl derivative

50

250

286.1

H3CO

O

C1913C1H17D3F3NO4 MW: 399.38 69.0 115.1

F 3C–COO

152.1

300

100

150

250 m/z



450

399.1

225.1

200

400

II-7-C-iv

13 N— CD3

338.0

0 50

350

300

350

400

450

170


Relative Int. (%)

100

Codeine, propionyl derivative

H3CO O

C21H25NO4 MW: 355.43

50

-

229.1 218.1

162.1

124.1

355.1

N CH 3

H 5C 2–COO

57.1

II-7-D-i

282.1

298.1

0 50

100

Relative Int. (%)

100

150

200

Codeine-d3, propionyl derivative

300

H3CO

127.1

57.1

II-7-D-ii

400 358.2

-

N CD 3

H 5C 2–COO

232.1 221.1

165.1

350

285.2

O

C21H22D3NO4 MW: 358.45

50

250

301.1

0 50

100

Relative Int. (%)

100

150

200

Codeine-d6, propionyl derivative

300

350

D3CO

288.2

O

C21H19D6NO4 MW: 361.47

50

250

165.1

127.1

361.2

-

N CD 3

H 5C 2–COO

57.1

II-7-D-iii

400

235.1 221.1

304.2


100

100

150

200

Codeine-13C

1-d3, propionyl derivative

286.2

O N H 5C 2–COO

166.1

128.1

57.1

300

H3CO

C2013C1H22D3NO4 MW: 359.44

50

250

350

II-7-D-iv

400 359.2

-13CD3 233.1

222.1

302.1

0 50

100

150

200

250

300

350

400

m/z

Relative Int. (%)

100

Codeine, pentafluoropropionyl derivative

282.1

II-7-E-i

O

C21H20F5NO4 MW: 445.38

50

H3CO

F 5 C 2 –COO

119.0

-

N CH 3

445.1

225.1

165.0


100

100

150

200

Codeine-d3, pentafluoropropionyl derivative

250

300 285.1

II-7-E-ii

400

F 5 C 2 –COO

119.0

450

500

H3CO O

C21H17D3F5NO4 MW: 448.40

50

350

-

448.1

N CD 3

225.0

152.1

0 50

100

150

200

250

300



350

400

450

500

171


Relative Int. (%)

100

288.1

Codeine-d6, pentafluoropropionyl derivative

451.1

O

C21H14D6F5NO4 MW: 451.42

50

D3CO

II-7-E-iii

-

N CD 3

F 5 C 2 –COO

119.0

152.1

228.1

0 50

100

Relative Int. (%)

100

150

Codeine-13C1-d3, pentafluoropropionyl derivative

200

250

350

400

450

500

286.1 H3CO

II-7-E-iv

O

C2013C1H17D3F5NO4 MW: 449.39 119.0 152.1

50

300

13 N— CD3

F 5 C 2 –COO

449.1

225.0

0 50

100

150

200

250

300

350

400

450

500


100

Codeine, heptafluorobutyryl derivative

282.1

II-7-F-i

495.1

O

C22H20F7NO4 MW: 495.39

50

H3CO

-

N CH 3

F 7 C 3 –COO

69.0

225.1

437.9

0 50

100

Relative Int. (%)

100

150

Codeine-d3, heptafluorobutyryl derivative

200

250

300

II-7-F-ii

400

450

H3CO

500

550

498.1

O

C22H17D3F7NO4 MW: 498.41

50

350

285.1

-

N CD 3

F 7 C 3 –COO

69.1

225.1

438.0

0 50

100

Relative Int. (%)

100

150

Codeine-d6, heptafluorobutyryl derivative

50

200

250

300

350

400

450

500

550

288.1

II-7-F-iii

D3CO O

C22H14D6F7NO4 MW: 501.42

F 7 C 3 –COO

69.0

501.1

-

N CD 3

228.1

441.1

0 50

100

Relative Int. (%)

100

150

Codeine-13C1-d3, heptafluorobutyryl derivative

50

62.1

200

250

II-7-F-iv

300

350

400

450

500

550

286.1 H3CO O

13

N— CD3

C2113C1H17D3F7NO4 MW: 499.40 152.0

F 7 C 3 –COO

224.0

499.1 438.0

0 50

100

150

200

250

300 m/z



350

400

450

500

550

172


Relative Int. (%)

100

Codeine, trimethylsilyl derivative

371.1

H3CO

II-7-G-i

O

50

C21H29NO3Si MW: 371.55

73.1

178.1

196.1

-

N CH 3

(H3C)3Si–O

234.1

146.0

280.1

94.1

313.1

343.1

0 50

100

Relative Int. (%)

100

150

200

Codeine-d3, trimethylsilyl derivative

250

300

350 374.2

H3CO

II-7-G-ii

O

50

C21H26D3NO3Si MW: 374.56

73.1

181.1

199.1

400

-

N CD 3

(H3C)3Si–O

237.1

149.1

283.1

97.1

313.1

346.1

0 50

100

Relative Int. (%)

100

150

200

Codeine-d6, trimethylsilyl derivative

50

300

350

D3CO

II-7-G-iii 184.1

199.1

400 377.2

O

C21H23D6NO3Si MW: 377.58

73.1

250

-

N CD 3

(H3C)3Si–O

237.1

149.1

316.1

288.1

97.1

349.2

0 50

100

Relative Int. (%)

100

150

200

Codeine-13C

1-d3, trimethylsilyl derivative

73.1

50

300

II-7-G-iv 182.1

C2013C1H26D3NO3Si MW: 375.56 150.1

250

350

H3CO O

200.1

400 375.2

13

N— CD3

238.2 (H3C)3Si–O

284.1

98.1

313.1

347.2

0 50

100

150

200

250

300

350

400

m/z

Relative Int. (%)

100

O

50

(H3C)3C(H3C)2Si–O

73.1 146.0

313.1

II-7-H-i

H3CO

Codeine, t-butyldimethylsilyl derivative

-

N CH 3

178.1

356.1 235.1

C24H35NO3Si MW: 413.64

285.1 413.2

0 50

100

Relative Int. (%)

100

150

200

O (H3C)3C(H3C)2Si–O

350

359.2 235.1

C24H32D3NO3Si MW: 416.65

285.1 416.2

0 50

100

150

200

250



450

Codeine-d3, t-butyldimethylsilyl derivative

-

181.1

400

313.1

N CD 3

73.1 149.1

300

II-7-H-ii

H3CO

50

250

300

350

400

450

173


Relative Int. (%)

100 D3CO O

50

(H3C)3C(H3C)2Si–O

73.1

149.1

II-7-H-iii

316.1

-

Codeine-d6, t-butyldimethylsilyl derivative 362.2

N CD 3

238.1 184.1

C24H29D6NO3Si MW: 419.66

288.1 419.3

0 50

100

Relative Int. (%)

100

150

200


350

13 N— CD3

235.1

450

1-d3, t-butyldimethylsilyl derivative

360.2

182.1

400 Codeine-13C

II-7-H-iv

73.1 150.1

300 313.1

H3CO

50

250

C2313C1H32D3NO3Si MW: 417.64

285.2 417.3

0 50

100

150

200

250 m/z



300

350

400

450

174

Figure II-8. Mass spectra of hydrocodone and its deuterated analogs (hydrocodone-d3, -d6): (A) underivatized; (B) ethyl-derivatized; (C) acetyl-derivatized; (D) TMS-derivatized; (E) t-BDMS-derivatized; (F) MA-derivatized; (G) HA/TMS-derivatized. Relative Int. (%)

100

Hydrocodone (CAS NO. 125-29-1) C18H21NO3 MW: 299.37

50

299.1

H3CO

HH

O

II-8-A-i

H

-

242.1

N CH 3 O

96.1

59.1

185.0

115.0

214.1

270.1 284.1


100

100

150

Hydrocodone-d3 (CAS NO. 136765-36-1) C18H18D3NO3 MW: 302.35

200

250

350 302.1

H3CO

HH

O

II-8-A-ii

H

-

N CD 3

50

O

99.1

62.1

300

242.1

185.0

115.0

273.1 287.1

214.0


100

100

150

Hydrocodone-d6

250

DD

O

350

II-8-A-iii

D

-

N CD 3 O

99.1

62.1

300 305.1

H3CO

C18H15D6NO3 MW: 305.32

50

200

245.1 188.0

115.0

217.1

276.1 287.1

0 50

Relative Int. (%)

100

100

Hydrocodone, ethyl derivative

150

70.0

115.1

300

350

327.3

O

298.2

-

N CH 3

190.2

77.2

250

H3CO

II-8-B-i

C20H25NO3 MW: 327.42

50

200 m/z

H 5C 2O

140.1

270.1

225.1

312.2

282.2


100

100

150

Hydrocodone-d3, ethyl derivative

II-8-B-ii

73.1

300

350 330.2

H3CO

301.2

-

N CD 3

193.2 115.1

77.0

250

O

C20H22D3NO3 MW: 330.44

50

200

H 5C 2O

270.2

225.2

143.1

312.2 285.2


100

100 Hydrocodone-d6, ethyl derivative

150

73.2

250 H3CO

II-8-B-iii

DD

304.2

-

H 5C 2O

143.2

273.2

228.1

77.1

350

D

N CD 3

193.2 115.1

300

333.3

O

C20H19D6NO3 MW: 333.45

50

200

315.2 288.2

0 50

100

150

200 m/z



250

300

350

175


Relative Int. (%)

100

H3CO

II-8-C-i

55.2

115.1

O

-

N CH 3

50

H 5COC–O

91.1

341.3

Hydrocodone, acetyl derivative

298.2

C20H23NO4 MW: 341.40 225.1

242.1 284.2

185.1

326.4

270.2

0 50

100

150

Relative Int. (%)

100

H3CO

115.1

II-8-C-ii

O

55.1

50 97.1

200

H 5COC–O

250

300

350 344.3

Hydrocodone-d3, acetyl derivative

-

N CD 3 C20H20D3NO4

301.4

242.2 285.2

MW: 344.42

185.1

225.1

326.1

273.1

0 50

100

150

Relative Int. (%)

100

II-8-C-iii

H3CO

115.1

O

55.1

50

H 5COC–O

97.1

200 DD

250

300

Hydrocodone-d6, acetyl derivative

D

350 347.4 304.3

C20H17D6NO4 N - CD 3 MW: 347.44 228.1 188.1

245.3

288.3 329.2

276.2

0 50

100

Relative Int. (%)

100 73.1

150

Hydrocodone, trimethylsilyl derivative

200 m/z

300

371.3

O

234.2

-

N CH 3 (H3C)3Si–O

184.1

115.1

350

H3CO

II-8-D-i

C21H29NO3Si MW: 371.54

50

250

356.2

314.2

282.2


100

100 73.1

150

Hydrocodone-d3, trimethylsilyl derivative

200

250

350

400 374.3

H3CO

II-8-D-ii

237.2 O

C21H26D3NO3Si MW: 374.56

50

300

-

N CD 3

(H3C)3Si–O

187.2

283.2

115.1

356.2

314.2


100

100 73.1

150

Hydrocodone-d6, trimethylsilyl derivative

200

250

II-8-D-iii

C21H23D6NO3Si MW: 377.58

50

H3CO

237.2

O

350

400 377.3

DD

D

-

N CD 3 (H3C)3Si–O

187.2

115.1

300

359.3

317.2

286.2

0 50

100

150

200

250 m/z



300

350

400

176


Relative Int. (%)

100

73.1

Hydrocodone, t-butyldimethylsilyl derivative

115.1

356.2

313.2

O

II-8-E-i

-

N CH 3

C24H35NO3Si MW: 413.63

50

H3CO

(H3C)3C(H3C)2Si–O

152.1

179.1

216.2

276.2 413.3

398.3

0 50

100

Relative Int. (%)

100

73.2

150

200

Hydrocodone-d3, t-butyldimethylsilyl derivative

115.1

152.0

300

H3CO

350

400

450

II-8-E-ii

313.2

O

C24H32D3NO3Si MW: 416.64

50

250

359.3

-

N CD 3

(H3C)3C(H3C)2Si–O

216.1

179.1

279.2

401.5

416.3

0 50

100

Relative Int. (%)

100

73.1

150

200

Hydrocodone-d6, t-butyldimethylsilyl derivative

115.2

152.1

H3CO

300

350

400

316.2

D

II-8-E-iii

-

N CD 3 (H3C)3C(H3C)2Si–O

179.2

216.1

279.3

100

Relative Int. (%)

100

150

200

Hydrocodone, methoxyimino derivative 57.1 71.2

50

419.4

401.2

0 50

450

362.3

DD

O

C24H29D6NO3Si MW: 419.66

50

250

C19H24N2O3 MW: 328.41 99.1 115.1

250 m/z

300

350

H3CO

II-8-F-i

O H3CO—N

400

450

328.2 297.2

-

N CH 3

207.0

271.1

240.1

313.1

0 50

100

Relative Int. (%)

100

150

Hydrocodone-d3, methoxyimino derivative

115.1

73.1

250

H3CO

H3CO—N

126.1

300

II-8-F-ii

O

C19H21D3N2O3 MW: 331.42

50

200

350 331.2

300.2

-

N CD 3

271.1 316.2

240.2

185.1

0 50

100

Relative Int. (%)

100

150

Hydrocodone-d6, methoxyimino derivative C19H18D6N2O3 MW: 334.44

50 73.1

85.1

115.1

200 H3CO O H3CO—N

126.1

149.1

250

DD

300

350 334.3

II-8-F-iii

303.2

D

-

N CD 3

188.2

243.1

274.2 316.2

0 50

100

150

200 m/z



250

300

350

177


Relative Int. (%)

100

Hydrocodone, hydroxylimino/trimethylsilyl derivative

50

297.2

H3CO

386.3

II-8-G-i

O

-

N CH 3

73.1 C21H30N2O3Si MW: 386.56 115.0

(H3C)3Si–O–N

185.1

329.1 371.2

213.0 282.2

0 50

100

Relative Int. (%)

100

150

200

73.1

350

H3CO

400 389.3

II-8-G-ii

O

C21H27D3N2O3Si MW: 389.58

300 300.2

Hydrocodone-d3, hydroxylimino/trimethylsilyl derivative

50

250

-

N CD 3 (H3C)3Si–O–N

185.1

115.1

213.1

329.2

285.2

374.2

0 50

100

Relative Int. (%)

100

150

Hydrocodone-d6, hydroxylimino/trimethylsilyl derivative

250

300

350

400

303.2 H3CO

DD

O

73.1 C21H24D6N2O3Si MW: 392.60

50

200

392.3

II-8-G-iii

D

-

N CD 3 (H3C)3Si–O–N

115.1

216.1

188.1

332.2

288.2

377.3

0 50

100

150

200

250 m/z



300

350

400

178

Figure II-9. Mass spectra of dihydrocodeine and its deuterated analogs (dihydrocodeine-d3, -d6): (A) underivatizedderivatized; (B) acetyl-derivatized; (C) TFA-derivatized; (D) propionyl-derivatized; (E) PFP-derivatized; (F) HFBderivatized; (G) TMS-derivatized; (H) t-BDMS-derivatized. Relative Int. (%)

100

II-9-A-i

O

C18H23NO3 MW: 301.38

50

301.2

H3CO

Dihydrocodeine (CAS NO. 125-28-0)

-

N CH 3

HO

164.1

70.1

115.1

244.1

185.1

284.2


100

100

150

250

300

C18H20D3NO3 MW: 304.40

II-9-A-ii

O

-

N CD 3

HO

167.1 115.0

73.0

350 304.1

H3CO

Dihydrocodeine-d3

50

200

287.1

245.1

185.0


100

100

150

Dihydrocodeine-d6

250

300

II-9-A-iii

O

-

N CD 3

HO

167.1 73.1

350 307.2

D3CO

C18H17D6NO3 MW: 307.42

50

200

290.2

248.1

188.1

115.1

0 50

Relative Int. (%)

100

100

150

Dihydrocodeine, acetyl derivative

70.1

250

H3CO

350

343.2

-

N CH 3

H 3C–COO

115.1

300

II-9-B-i

O

C20H25NO4 MW: 343.42

50

200 m/z

284.2

226.1

300.1

185.0

146.1


100

100

150

200

Dihydrocodeine-d3, acetyl derivative

300

H3CO

350

II-9-B-ii

O

C20H22D3NO4 MW: 346.44

50

250

400

346.1

-

N CD 3

H 3C–COO

287.1

303.1

226.0

73.0

115.0

185.0

149.0


100

100

150

200

Dihydrocodeine-d6, acetyl derivative

73.1

-

N CD 3

H 3C–COO

149.1

350

II-9-B-iii

O

115.1

300

D3CO

C20H19D6NO4 MW: 349.45

50

250

227.1

290.2

400

349.2

306.2

183.1

0 50

100

150

200

250 m/z



300

350

400

179


Relative Int. (%)

100

Dihydrocodeine, trifluoroacetyl derivative

59.1

II-9-C-i

O

C20H22F3NO4 MW: 397.39

50

397.1

H3CO

-

N CH 3

F 3C–COO

284.1

185.0

115.1

300.1

227.1

340.1


100

100

150

200

Dihydrocodeine-d3, trifluoroacetyl derivative

62.1

300

350

450

II-9-C-ii

O

-

N CD 3

F 3C–COO

287.1

185.0

115.0

400 400.1

H3CO

C20H19D3F3NO4 MW: 400.41

50

250

303.1

227.0

340.0


100

100

150

200

Dihydrocodeine-d6, trifluoroacetyl derivative

300

350

400

450 403.2

D3CO

II-9-C-iii

O

C20H16D6F3NO4 MW: 403.42 62.1 115.1

50

250

-

N CD 3

F 3C–COO

290.2

188.1

306.2

230.1

343.1

0 50

Relative Int. (%)

100

100

150

200

Dihydrocodeine, propionyl derivative

70.1

300

400

450

II-9-D-i

O

-

N CH 3

H 5C 2–COO

284.1

300.1

226.1

199.1

146.1

350

357.2

H3CO

C21H27NO4 MW: 357.44

50

250 m/z


100

100

150

200

Dihydrocodeine-d3, propionyl derivative

73.1

300

400

II-9-D-ii

O

-

N CD 3

H 5C 2–COO

303.2

287.2 226.1

199.1

149.1

350 360.2

H3CO

C21H24D3NO4 MW: 360.46

50

250


100

100

150

200

Dihydrocodeine-d6, propionyl derivative

73.2

300

D3CO

H 5C 2–COO

350

400 363.2

II-9-D-iii

O

C21H21D6NO4 MW: 363.48

50

250

-

N CD 3

306.2

290.2 229.1

149.1

202.1

0 50

100

150

200

250 m/z



300

350

400

180


Relative Int. (%)

100

Dihydrocodeine, pentafluoropropionyl derivative

O

C21H22F5NO4 MW: 447.40

50

284.1 185.0

119.0

59.1

447.1

H3CO

II-9-E-i

-

N CH 3

F 5 C 2 –COO

300.1

227.1

390.1

432.1

0 50

100

Relative Int. (%)

100

150

200

Dihydrocodeine-d3, pentafluoropropionyl derivative

250

300

350

400

O

62.1

287.1 185.0

118.9

-

N CD 3

F 5 C 2 –COO

303.1

227.0

500 450.1

H3CO

II-9-E-ii

C21H19D3F5NO4 MW: 450.41

50

450

390.0

435.1

0 50

100

Relative Int. (%)

100

150

200

Dihydrocodeine-d6, pentafluoropropionyl derivative

250

300

62.1

400

188.1

-

N CD 3

F 5 C 2 –COO

306.2

230.1

500 453.2

O

290.2

119.0

450

D3CO

II-9-E-iii

C21H16D6F5NO4 MW: 453.43

50

350

393.1

435.1

0 50

100

150

200

250

300

350

400

450

500


100

Dihydrocodeine, heptafluorobutyryl derivative

O

C22H22F7NO4 MW: 497.40

50

F 7 C 3 –COO

284.1

59.1

497.1

H3CO

II-9-F-i

146.1

185.1

227.1

-

N CH 3

300.1

440.0 482.0


100

100

150

200

Dihydrocodeine-d3, heptafluorobutyryl derivative C22H19D3F7NO4 MW: 500.42 62.1

50

250

300

350

400

F 7 C 3 –COO

-

N CD 3

303.1

227.0

550

500.1

O

287.1 185.0

500

H3CO

II-9-F-ii

149.0

450

440.0 485.1


100

100

150

200

Dihydrocodeine-d6, heptafluorobutyryl derivative

250

62.1

350

400

290.2 188.1

500

F 7 C 3 –COO

-

N CD 3

306.2

227.1

550 503.1

O

149.1

450

D3CO

II-9-F-iii

C22H16D6F7NO4 MW: 503.44

50

300

443.0 485.1

0 50

100

150

200

250

300 m/z

350



400

450

500

550

181


Relative Int. (%)

100

Dihydrocodeine, trimethylsilyl derivative

O

C21H31NO3Si MW: 373.56

50

(H3C)3Si–O

146.1

73.1

373.2

H3CO

II-9-G-i -

N CH 3

236.1

178.1

315.1

282.1

358.1

0 50

100

Relative Int. (%)

100

150

200

Dihydrocodeine-d3, trimethylsilyl derivative

300

350

O (H3C)3Si–O

149.0

73.0

400 376.2

H3CO

C21H28D3NO3Si MW: 376.58

50

250

II-9-G-ii -

N CD 3

239.1 285.1

181.0

315.1 361.1

0 50

100

Relative Int. (%)

100

150

200

Dihydrocodeine-d6, trimethylsilyl derivative

300

350

O (H3C)3Si–O

73.1

149.1

400 379.2

D3CO

C21H25D6NO3Si MW: 379.60

50

250

II-9-G-iii -

N CD 3

239.1

184.1

318.1

288.1

364.2

0 50

100

150

200

250

300

350

400


100

H3CO

Dihydrocodeine, t-butyldimethylsilyl derivative

50 73.1

O

C24H37NO3Si MW: 415.64

(H3C)3C(H3C)2Si–O

315.1 358.2

-

N CH 3

207.0

II-9-H-i

297.1

282.1

146.1

415.2

0 50

100

Relative Int. (%)

100

150

200

Dihydrocodeine-d3, t-butyldimethylsilyl derivative

300


350 315.0

H3CO

C24H34D3NO3Si MW: 418.65

50

250

400 361.1

450

II-9-H-ii

297.0

-

N CD 3

282.0

73.0

149.0

418.2

204.0

0 50

100

Relative Int. (%)

100

150

200

Dihydrocodeine-d6, t-butyldimethylsilyl derivative

50

73.1

250

300

D3CO O

C24H31D6NO3Si MW: 421.67

(H3C)3C(H3C)2Si–O

400 364.2

450

II-9-H-iii

300.1

-

N CD 3

207.0

149.1

350 318.1

282.1 421.3

0 50

100

150

200

250 m/z



300

350

400

450

182

Figure II-10. Mass spectra of oxycodone and its deuterated analogs (oxycodone-d3, -d6): (A) underivatized; (B) acetylderivatized; (C) [acetyl]2-derivatized; (D) propionyl-derivatized; (E) TMS-derivatized; (F) [TMS]2-derivatized; (G) t-BDMS-derivatized; (H) [t-BDMS]2-derivatized; (I) MA-derivatized; (J) MA/propionyl-derivatized; (K) MA/TMSderivatized; (L) HA/[propionyl]2-derivatized; (M) HA/[TMS]2-derivatized; (N) HA/ethyl/propionyl-derivatized. Relative Int. (%)

100

315.1

Oxycodone (CAS NO. 76-42-6)

H3CO

C18H21NO4 MW: 315.36

50

O

-

N CH 3

O

70.0

115.1

II-10-A-i

OH

230.1

201.0

140.0

258.0


100

100

150

Oxycodone-d3 (CAS NO. 160227-46-3)

H3CO O

C18H18D3NO4 MW: 318.38

50

200

250

300

350 318.1

OH

II-10-A-ii

-

N CD 3

233.1

O

70.0

115.1

204.0

140.0

261.1


100

100

150

Oxycodone-d6 (CAS NO. 152477-91-3)

D3CO O

C18H15D6NO4 MW: 321.40

50

200

250

115.0

350 321.2

OH

II-10-A-iii

-

N CD 3

236.1

O

73.1

300

261.1

204.0

143.1

0 50

Relative Int. (%)

100

100

150

Oxycodone, acetyl derivative

H3CO

C20H23NO5 MW: 357.40

50

200 m/z

O

O

250

300

350

357.2

II-10-B-i

OOC–-CH3

314.1

-

N CH 3

212.1

115.1

230.1

298.1

342.1


100

100

150

250

300

350

400 360.2

Oxycodone-d3, acetyl derivative

H3CO

C20H20D3NO5 MW: 360.42

50

200

O

O

II-10-B-ii

OOC–CH 3

317.1

-

N CD 3

215.1

115.1

233.1

301.2

342.1


100

100

150

Oxycodone-d6, acetyl derivative

D3CO O

C20H17D6NO5 MW: 363.44

50

200

250

300

350

400 363.2

II-10-B-iii

OOC–CH 3

320.2

-

N CD 3

O

215.1

115.1

236.2

304.2

345.1

0 50

100

150

200

250 m/z



300

350

400

183


Relative Int. (%)

100

Oxycodone, di-acetyl derivative

H3CO O

C22H25NO6 MW: 399.44

50

399.2

II-10-C-i

OOC–CH 3

-

N CH 3

H 3C–COO

356.1 240.1

115.1

296.1

280.1

384.1

340.1


100

100

150

Oxycodone-d3, di-acetyl derivative

200 H3CO O

C22H22D3NO6 MW: 402.45

50

250

300

350

400

450 402.2

II-10-C-ii

OOC–CH 3

-

N CD 3

H 3C–COO

359.1

243.1 299.1

384.1

343.1

283.1

115.1


100

100

150

200

300

350

400

450 405.2

Oxycodone-d6, di-acetyl derivative

D3CO

C22H19D6NO6 MW: 405.47

50

250

O

II-10-C-iii

OOC–CH 3

-

N CD 3

362.2 243.1

H 3C–COO

302.1 286.1

115.1

387.1

346.2

0 50

Relative Int. (%)

100

100

Oxycodone, propionyl derivative

150

200

H3CO

C21H25NO5 MW: 371.43

50

O

250 m/z

300

350

400

371.1

II-10-D-i

OOC–C 2H 5

450

314.1

-

N CH 3

O

212.1

57.1

240.1

298.1 356.1


100

100 Oxycodone-d3, propionyl derivative

150 H3CO

C21H22D3NO5 MW: 374.45

50

200

O

250

300

350

II-10-D-ii

OOC–C 2H 5

400 374.2

317.1

-

N CD 3

O

215.1

57.1

244.1

301.1

356.1


100

100 Oxycodone-d6, propionyl derivative

150 D3CO

C21H19D6NO5 MW: 377.46

50

200

O

250

300

350

377.2

II-10-D-iii

OOC–C 2H 5

400

320.1

-

N CD 3

O

215.1 236.2

57.1

304.2

359.1

0 50

100

150

200

250 m/z



300

350

400

184


Relative Int. (%)

100

Oxycodone, trimethylsilyl derivative

H3CO O

C21H29NO4Si MW: 387.54

50

387.2

II-10-E-i

O–Si(CH3)3

-

N CH 3

O

73.1

372.2

229.1 273.1

214.1

115.1

330.1

0 50

100

Relative Int. (%)

100

150

200

Oxycodone-d3, trimethylsilyl derivative

250 H3CO

50

O

73.1

400

450

390.2

II-10-E-ii

-

N CD 3

232.1

375.2 276.1

214.1

115.1

350

O–Si(CH3)3

O

C21H26D3NO4Si MW: 390.56

300

333.1

0 50

100

Relative Int. (%)

100

150

200

Oxycodone-d6, trimethylsilyl derivative

250 D3CO O

C21H23D6NO4Si MW: 393.58

50

300

350

400

II-10-E-iii

O–Si(CH3)3

450

393.2

-

N CD 3

O

73.1

236.1

217.1

115.1

378.2

276.1

333.1

0 50

100

Relative Int. (%)

100

150

200

Oxycodone, di-trimethylsilyl derivative 73.1

H3CO O

C24H37NO4Si2 MW: 459.73

50

250 m/z

300

350

450

459.2

II-10-F-i

O–Si(CH3)3

-

N CH 3

(H3C)3Si–O

242.1

400

444.2

312.1

297.1

368.2

0 50

100

Relative Int. (%)

100

150

200

Oxycodone-d3, di-trimethylsilyl derivative 73.1

50

250 H3CO O

C24H34D3NO4Si2 MW: 462.74

300

350

400

500 462.2

II-10-F-ii

O–Si(CH3)3

-

N CD 3

(H3C)3Si–O

242.1

450

297.1

315.1

371.2

447.2

0 50

100

Relative Int. (%)

100

150

200

Oxycodone-d6, di-trimethylsilyl derivative 73.1

50

250 D3CO O

C24H31D6NO4Si2 MW: 465.76

300

350

400

450 465.3

II-10-F-iii

O–Si(CH3)3

500

-

N CD 3

(H3C)3Si–O

315.1

242.1 297.1

374.2

450.2

0 50

100

150

200

250

300 m/z



350

400

450

500

185


Relative Int. (%)

100

Oxycodone, t-butyldimethylsilyl derivative

50

372.1

II-10-G-i

H3CO O

C24H35NO4Si 73.1 MW: 429.62

O–Si(CH3)2C(CH3)3

-

N CH 3

O

216.1

179.1

327.1

301.1

429.2

0 50

100

Relative Int. (%)

100

150

200

Oxycodone-d3, t-butyldimethylsilyl derivative

50

250

II-10-G-ii

300

350

400

450

375.2 H3CO O

C24H32D3NO4Si 73.1 MW: 432.64

O–Si(CH3)2C(CH3)3

-

N CD 3

O

216.1

182.1

304.1

330.1 432.2

0 50

100

Relative Int. (%)

100

150

200

Oxycodone-d6, t-butyldimethylsilyl derivative 73.1

50

250

II-10-G-iii

300

350

D3CO O

C24H29D6NO4Si MW: 435.66

-

N CD 3

304.1

216.1

330.1 435.3

0 50

Relative Int. (%)

100

100

73.1

150

200

Oxycodone, di-t-butyldimethylsilyl derivative

II-10-H-i

250 m/z

300

H3CO O

50

C30H49NO4Si2 MW: 543.89

225.0

133.0

450

O–Si(CH3)2C(CH3)3

O

185.1

400 378.2

350

400

450

486.3 O–Si(CH3)2C(CH3)3

-

N CH 3

(H3C)3C(H3C)2Si–O

412.4

371.2

530.0

543.2


100

100 73.1

150

200

Oxycodone-d3, di-t-butyldimethylsilyl derivative

250

II-10-H-ii

350

226.1

133.2

400

450

Relative Int. (%)

100

100 73.1

50

150

-

N CD 3

(H3C)3C(H3C)2Si–O

415.3

374.0

533.1

200

Oxycodone-d6, di-t-butyldimethylsilyl derivative C30H43D6NO4Si2 MW: 549.92

250

II-10-H-iii

300

350

D3CO O

400

450

500

150

-

N CD 3

(H3C)3C(H3C)2Si–O

420.0

377.3

200

250

300 m/z



550

492.4

549.3 535.2

0 100

546.4

O–Si(CH3)2C(CH3)3

233.0

147.0

50

550

O–Si(CH3)2C(CH3)3

0 50

500 489.3

H3CO O

C30H46D3NO4Si2 MW: 546.90

50

300

350

400

450

500

550

186


100

Oxycodone, methoxyimino derivative

II-10-I-i

OH

O

C19H24N2O4 MW: 344.40

50

344.2

H3CO

-

N CH 3

H3CO—N

70.1

230.2

127.1

115.0

256.1

313.2

287.1

0 50

100

100

150

200

250

350

400

347.2

Oxycodone-d3, methoxyimino derivative

H3CO

C19H21D3N2O4 MW: 347.42

50

300

II-10-I-ii

OH

O

-

N CD 3

H3CO—N

70.1

115.1

233.1

128.1

259.1

316.2

288.1

0 50

100

Relative Int. (%)

100

150

200

Oxycodone-d6, methoxyimino derivative

250 D3CO

C19H18D6N2O4 MW: 350.44

50 73.1

OH

O

300

350 350.3

II-10-I-iii

-

N CD 3

H3CO—N

115.1

400

236.2

127.1

259.1

319.2

290.1

0 50

100

150

200

250

300

350

400


100

Oxycodone, methoxyimino/propionyl H3CO derivative

O

50

57.1 C22H28N2O5 MW: 400.47

400.3 O–CO(C2H5)

II-10-J-i

230.2

343.2

-

N CH 3

115.2 H3CO—N

240.1

295.0

369.3


100

50

100

150

200

Oxycodone-d3, methoxyimino/propionyl H3CO derivative C22H25D3N2O5 57.1 MW: 403.49

O

250

300

350

400

450 403.3

II-10-J-ii

O–CO(C2H5)

-

N CD 3

233.2

H3CO—N

117.0

243.1

346.3 298.2

372.1


100

100

150

200

Oxycodone-d6, methoxyimino/propionyl D3CO derivative O

C22H22D6N2O5 MW: 406.50 131.0 58.7

50

250

300

350

400

450 406.4

II-10-J-iii

O–CO(C2H5)

-

N CD 3

349.3

236.2

H3CO—N

248.4

301.0 376.3

0 50

100

150

200

250 m/z



300

350

400

450

187


Relative Int. (%)

100

Oxycodone, methoxyimino/trimethylsilyl derivative

O–Si(CH3)3

O

C H N O Si 73.1 22 32 2 4 MW: 416.59

50

416.3

H3CO

II-10-K-i 229.1

214.1

-

N CH 3

H3CO—N

295.2

401.2

359.2

326.1

0 50

100

Relative Int. (%)

100

150

200

300

350

400

450 419.3

Oxycodone-d3, methoxyimino/trimethylsilyl derivative

50

250 H3CO

II-10-K-ii

O–Si(CH3)3

O

C H D N O Si 73.1 22 29 3 2 4 MW: 419.60

232.1

214.1

-

N CD 3

H3CO—N

298.2

404.3

362.2

329.2

0 50

100

Relative Int. (%)

100

150

200

73.1

300

350

400

450 422.3

Oxycodone-d6, methoxyimino/trimethylsilyl derivative

50

250 D3CO

II-10-K-iii

O–Si(CH3)3

O

C22H26D6N2O4Si MW: 422.62

235.2

-

N CD 3

H3CO—N

217.1

407.3

362.2

332.2

301.2

0 50

Relative Int. (%)

100

100

Oxycodone, hydroxylimine/ di-propionyl derivative

50

150

139.1

200

250 m/z

300

350

400

450

H3CO

II-10-L-i

O–CO(C2H5)

O

C24H30N2O6 MW: 458.51

195.1

-

N CH 3

295.1

230.2 272.1

313.2

H5C2OC—O—N

328.2 369.3

442.3

386.3 402.2


100

100 Oxycodone-d3, hydroxylimine/ di-propionyl derivative

50

150 139.1

200

250

300

350

400

450 H3CO

II-10-L-ii 298.2 331.2

C24H27D3N2O6 MW: 461.53

316.2

275.1

195.2

O–CO(C2H5)

O

233.2 372.2

500

-

N CD 3

H5C2OC—O—N

445.2

389.3 405.2


100

100 Oxycodone-d6, hydroxylimine/ di-propionyl derivative

50

150 142.1

200

250

300

350

400

450 D3CO

II-10-L-iii

301.2

C24H24D6N2O6 MW: 464.55

334.2 375.1 319.3

278.1

198.1

O–CO(C2H5)

O

236.2

H5C2OC—O—N

391.3

500

-

N CD 3

448.3

408.2

0 50

100

150

200

250

300 m/z



350

400

450

500

188


Relative Int. (%)

100

50

C24H38N2O4Si2 MW: 474.74

474.3

H3CO

II-10-M-i

Oxycodone, hydroxylimino/ di-trimethylsilyl derivative

73.1

O–Si(CH3)3

O

229.1

214.1

-

N CH 3

(H3C)3SiO—N

459.3 401.2

385.2

295.1

417.2

0 50

100

Relative Int. (%)

100

150

200

250

Oxycodone-d3, hydroxylimino/ di-trimethylsilyl derivative

73.1

50

300

II-10-M-ii

350

450

O–Si(CH3)3

-

N CD 3

(H3C)3SiO—N

232.1 214.1

500 477.3

H3CO O

C24H35D3N2O4Si2 MW: 477.76

400

462.3 404.3

388.3

298.2

420.2

0 50

100

Relative Int. (%)

100

150

200

250

Oxycodone-d6, hydroxylimino/ di-trimethylsilyl derivative

73.1

50

300

II-10-M-iii

350

D3CO

450

-

N CD 3

(H3C)3SiO—N

235.2 217.1

500 480.3

O–Si(CH3)3

O

C24H32D6N2O4Si2 MW: 480.78

400

465.3 407.3

391.3

301.2

420.3

0 50

100

150

200

250

300

350

400

450

500


100

Oxycodone, hydroxylimino/ethyl/propionyl derivative

II-10-N-i

O

C23H30N2O5 MW: 414.49

50

230.1

57.1 185.1

115.1

H3CO

414.3 O–CO(C2H5)

-

N CH 3

357.2

H5C2O—N

340.3

295.2

399.3

0 50

100

Relative Int. (%)

100

150

200

II-10-N-ii

Oxycodone-d3, hydroxylimine/ethyl/propionyl derivative 57.1

50

250

H3CO O

233.2

C23H27D3N2O5 MW: 417.51 115.1

300

350

450 417.3

O–CO(C2H5)

-

N CD 3

H5C2O—N

360.2

344.3

298.2

184.0

400

399.4

0 50

100

Relative Int. (%)

100

150

200

II-10-N-iii

Oxycodone-d6, hydroxylimino/ethyl/propionyl derivative

50 57.1

250

300 D3CO O

236.2

C23H24D6N2O5 MW: 420.53

350

400

450 420.3

O–CO(C2H5)

-

N CD 3

363.3

H5C2O—N

301.2

202.1

128.1

347.2

402.2

350

400

0 50

100

150

200

250 m/z

300



450

189

Figure II-11. Mass spectra of noroxycodone and its deuterated analogs (noroxycodone-d3): (A) underivatized; (B) [acetyl]2derivatized; (C) [TFA]3-derivatized; (D) propionyl-derivatized; (E) [PFP]2-derivatized; (F) [HFB]2-derivatized; (G) [TMS]2derivatized; (H) [TMS]3-derivatized; (I) MA/ethyl-derivatized; (J) MA/acetyl-derivatized; (K) MA/[TFA]2-derivatized; (L) MA/propionyl-derivatized; (M) MA/PFP-derivatized; (N) MA/[HFB]2-derivatized; (O) MA/[TMS]2-derivatized; (P) MA/tBDMS-derivatized; (Q) MA/ethyl/propionyl-derivatized; (R) MA/ethyl/TMS-derivatized; (S) MA/ethyl/t-BDMS-derivatized; (T) MA/acetyl/TMS-derivatized; (U) MA/propionyl/TMS-derivatized; (V) HA/[ethyl]2/TMS-derivatized. relative Int. (%)

100

Noroxycodone

H3CO

C17H19NO4 MW: 301.34

50

II-11-A-i

OH

O

-

N H

216.0

O

188.0 175.0

126.0

115.0

301.1

258.0


100

100

150

Noroxycodone-d3

D3CO

C17H16D3NO4 MW: 304.36

200

250

300

II-11-A-ii

OH

O

-

N H

50

350 304.1

219.0

O

126.0

115.0

191.0

178.0

261.1


100

100

150

Noroxycodone, di-acetyl derivative

H3CO

250

300

239.0

325.1

350

II-11-B-i

269.0

N –COCH 3

282.0

O

115.0

55.1 73.1

207.0

O–COCH 3

O

C21H23NO6 MW: 385.41

50

200 m/z

385.1 300.0

153.2


100

100

150

Noroxycodone-d3, di-acetyl derivative

115.1

55.1 73.0

250

300

350

242.0

328.1

O–COCH 3

O

C21H20D3NO6 MW: 388.43

50

200

D3CO

N –COCH 3

207.0

400

II-11-B-ii

272.1 388.1

285.1

O

303.1

155.1

0 50

100

150

200

250

300

350

400


100

69.0

Noroxycodone, tri-trifluoroacetyl derivative

H3CO

C23H16F9NO7 MW: 589.36

50

97.0

O

336.0

152.0

362.0

237.1

II-11-C-i

O–COCF 3 N –COCF 3

589.0

F 3C–COO

475.0


100

100 69.0

150

200

250

300

350

400

Noroxycodone-d3, tri-trifluoroacetyl derivative

D3CO O

C23H13D3F9NO7 MW: 592.38

50

97.0

450

339.0

152.0

500

550

600

650

II-11-C-ii


592.1

365.1 F C–COO 3 479.0

240.1

0 50

100

150

200

250

300

350 m/z



400

450

500

550

600

650

190


Relative Int. (%)

100

Noroxycodone, propionyl derivative

201.1

C20H23NO5 MW: 357.40

50

185.1

OH

O

239.1

57.1

357.1

H3CO

II-11-D-i

-

N COC 2H 5

258.1 O

228.1

301.1

115.1


100

100

150

Noroxycodone-d3, propionyl derivative

200

350

188.1

OH

O

242.1

400 360.1

D3CO

204.1

57.1

300

II-11-D-ii

C20H20D3NO5 MW: 360.42

50

250

-

N COC 2H 5

261.1 O

231.1

304.1

115.1

0 50

100

150

200

250

300

350

400


100

239.0

II-11-E-i

105.0

H3CO O

50

163.0

77.0

119.0

Noroxycodone, di-pentafluoropropionyl derivative

O–COC 2 F 5 N –COC 2 F 5

C23H17F10NO6 MW: 593.37 593.0

O

211.0

430.1

0 50

100

150

Relative Int. (%)

100

200

250

300

350 D3CO

105.0

O

50 77.0

450

500

242.0

II-11-E-ii 119.0

400

163.0 214.1

550

600

Noroxycodone-d3, di-pentafluoropropionyl derivative

O–COC 2 F 5

C23H14D3F10NO6 MW: 596.39 596.0

N –COC 2 F 5

O

433.1

0 50

100

150

200

250

300

350

400

450

500

550

600


100

239.0

II-11-F-i

H3CO O

50 69.0

169.0

211.0

Noroxycodone, di-heptafluorobutyryl derivative

O–COC 3 F 7

C25H17F14NO6 MW: 693.38

N –COC 3 F 7

O

480.1

693.1

0 50

100

150

200

Relative Int. (%)

100

250

300

350

242.0

II-11-F-ii

400 D3CO O

50 69.0

169.0

450

500

550

650

700

Noroxycodone-d3, di-heptafluorobutyryl derivative

O–COC 3 F 7 N –COC 3 F 7

C25H14D3F14NO6 MW: 696.40

O

214.1

600

696.1

483.0

0 50

100

150

200

250

300

350

400

450

m/z



500

550

600

650

700

191


Relative Int. (%)

100

73.1

Noroxycodone, di-trimethylsilyl derivative

H3CO

C23H35NO4Si2 MW: 445.70

50

O–Si(CH3)3

O

445.1

II-11-G-i

N –Si(CH3)3

O

312.0

297.0

226.1

430.1

354.1


100

100 73.1

150

200

250

Noroxycodone-d3, di-trimethylsilyl derivative

D3CO

350

O–Si(CH3)3

O

C23H32D3NO4Si2 MW: 448.72

50

300

400

450

500

450

500

448.2

II-11-G-ii

N –Si(CH3)3

O

229.0

315.0

297.0

433.1

357.2

0 50

100

150

200

250

300

350

400


100

Noroxycodone, tri-trimethylsilyl derivative

73.0

H3CO

C26H43NO4Si3 MW: 517.88

50 102.0

O–Si(CH3)3

O

128.1

207.0

II-11-H-i

N –Si(CH3)3

445.1

(H3C)3Si–O

517.2

373.0


100

100

150

200

250

Noroxycodone-d3, tri-trimethylsilyl derivative

73.1

D3CO

128.1

102.1

350 O–Si(CH3)3

O

C26H40D3NO4Si3 MW: 520.90

50

300

400

450

500

550

II-11-H-ii

N –Si(CH3)3

448.2

(H3C)3Si–O

520.2

207.0

376.1

0 50

100

150

Relative Int. (%)

100

200

Noroxycodone, methoxyimino/ethyl derivative

84.1

300 m/z

350

400

450

500

O–C 2 H 5

550

358.2

II-11-I-i

H3CO O

C20H26N2O4 MW: 358.43

50

250

343.2

NH

H 3CO–N

244.2

115.0

327.2

287.0 299.1

0 50

100

Relative Int. (%)

100

150 Noroxycodone-d3, methoxyimino/ethyl derivative

50

C20H23D3N2O4 MW: 361.45 84.1

200

250

D3CO

O–C 2 H 5

O

300

350 361.2

II-11-I-ii 346.2

NH

H 3CO–N

247.1

115.1

400

290.1

330.2 302.2

0 50

100

150

200

250 m/z



300

350

400

192


Relative Int. (%)

100

Noroxycodone, methoxyimino/acetyl derivative

NH

H 3CO–N

217.1

286.1 341.1

184.0

124.8

60.8

II-11-J-i

O–COCH 3

O

C20H24N2O5 MW: 372.42

50

372.2

299.1

H3CO

354.2

329.1


100

100

150

C20H21D3N2O5 64.8 MW: 375.43

250

300

350

400 375.2

Noroxycodone-d3, methoxyimino/acetyl derivative

50

200

D3CO

O–COCH 3

O

289.1

NH

129.1 H3CO–N

II-11-J-ii

302.2

220.1

344.1

187.9

326.2

355.8

0 50

100

150

200

250

300

350

400


100

Noroxycodone, methoxyimino/di-trifluoroacetyl derivative

69.1

H3CO O

C22H20F6N2O6 MW: 522.39

50 97.0

268.1

II-11-K-i


H 3CO–N

377.2

126.0

491.3

409.2

522.1


100

100 69.1

150

200

250

300

Noroxycodone-d3, methoxyimino/di-trifluoroacetyl derivative

350 D3CO

C22H17D3F6N2O6 MW: 525.41 97.0 126.0

271.2

450

500

550

II-11-K-ii

O–COCF 3

O

50

400

N –COCF 3

H 3CO–N

380.3

494.0

412.3

525.2

0 50

Relative Int. (%)

100

100

150

200

Noroxycodone, methoxyimino/propionyl 57.1 derivative

50

C21H26N2O5 MW: 386.44

250

H3CO O

300 m/z

350

450 299.2

500

550

II-11-L-i

O–COC 2H 5

386.3

NH

286.2

217.1

H 3CO–N

115.1

400

238.1

185.1

268.1

355.3 368.1 329.2 337.2


100

100

150

Noroxycodone-d3, methoxyimino/propionyl 57.1 derivative C21H23D3N2O5 MW: 389.46

50

200 D3CO O

250

350 302.2

O–COC 2H 5

400

II-11-L-ii 389.3

NH

220.2

H 3CO–N

271.2

289.2 358.2 371.3 332.3 340.3

241.1

188.1

115.1

300

0 50

100

150

200

250 m/z



300

350

400

193


Relative Int. (%)

100

119.1

II-11-M-i

217.1

50 144.2

O–COC 2 F 5

O

NH

H 3CO–N

C21H21F5N2O5 MW: 476.39 286.2 253.0

187.1 69.1

H3CO

Noroxycodone, methoxyimino/pentafluoropropionyl derivative

476.3 445.2

0 50

100

150

Relative Int. (%)

100

119.0

200

250

II-11-M-ii 220.1

50

350

400

Noroxycodone-d3, methoxyimino/pentafluoropropionyl derivative

144.0

450

D3CO

500

O–COC 2 F 5

O

C21H18D3F5N2O5 MW: 479.41 255.3 286.2

190.2 69.0

300

NH

H 3CO–N

479.2

448.4

0 50

100

150

200

250

300

350

400

450

500


100

268.1

II-11-N-i

H3CO

69.1

169.1

O–COC 3 F 7

O

50

Noroxycodone, methoxyimino/di-heptafluorobutyryl derivative C26H20F14N2O6 MW: 722.42

N –COC 3 F 7

238.1 H 3CO–N

477.2

115.1

722.3

0 50

100

150

200

250

Relative Int. (%)

100

300

350

400

271.2

D3CO

69.1 241.2

500

550

600

II-11-N-ii

O–COC 3 F 7

O

169.0

50

450

650

N –COC 3 F 7

H 3CO–N

750

C26H17D3F14N2O6 MW: 725.44 725.4

480.2

115.1

700

Noroxycodone-d3, methoxyimino/di-heptafluorobutyryl derivative

0 50

Relative Int. (%)

100

100

150

200

250

300

350

400 m/z

Noroxycodone, methoxyimino/di-trimethylsilyl derivative

73.1

H3CO

100.1

147.1

500

600

II-11-O-i

700

750

474.3

359.2 287.1

275.2

650

N –Si(CH3)3

H 3CO–N

188.1

550

O–Si(CH3)3

O

C24H38N2O4Si2 MW: 474.74

50

450

443.3

459.2


100

100 73.1

150

200

250

Noroxycodone-d3, methoxyimino/di-trimethylsilyl derivative

50

D3CO

147.1

350 O–Si(CH3)3

O

C24H35D3N2O4Si2 MW: 477.76 100.1

300

278.2

450

II-11-O-ii

500

477.3

N –Si(CH3)3

H 3CO–N

191.1

400

362.2 290.2

446.3

462.3

0 50

100

150

200

250

300 m/z



350

400

450

500

194


Relative Int. (%)

100

75.1 Noroxycodone, methoxyimino/t-butyldimethylsilyl derivative C24H36N2O4Si MW: 444.64

50

H3CO

O–Si(CH3)2C(CH3)3

O

II-11-P-i

NH

H 3CO–N

387.3

302.2

226.2

272.3

325.2

355.2

444.0

0 50

100

Relative Int. (%)

100

150

200

75.1 Noroxycodone-d3, methoxyimino/t-butyldimethylsilyl derivative C24H33D3N2O4Si MW: 447.66

50

250 D3CO

300

350

O–Si(CH3)2C(CH3)3

O

400

450

II-11-P-ii

NH

390.3

305.3

H 3CO–N

229.0

275.2

331.1

360.3

447.0

0 50

100

Relative Int. (%)

100

150

200

Noroxycodone, methoxyimino/ethyl/ propionyl derivative

50

H3CO

350

400

450

414.3

II-11-Q-i

N –COC 2 H 5

357.2

244.1

H 3CO–N

57.1

300

O–C 2 H 5

O

C23H30N2O5 MW: 414.49

250 m/z

309.2

71.2

399.2

325.1 341.1


100

100

150

200

300

350

400

450 417.3

Noroxycodone-d3, methoxyimino/ethyl/ propionyl derivative

50

250

D3CO

C23H27D3N2O5 57.1 MW: 417.51

II-11-Q-ii

O–C 2 H 5

O

N –COC 2 H 5

360.3

247.2

H 3CO–N

312.2

71.1

328.2 344.2

402.3

0 50

100

Relative Int. (%)

100

150

200

250 m/z H3CO

Noroxycodone, methoxyimino/ethyl/ trimethylsilyl derivative

50

73.1

300

O

C23H34N2O4Si MW: 430.61

350

O–Si(CH3)3

400

430.3

II-11-R-i

N –C 2 H 5

H 3CO–N

188.1 199.1

228.1

450

415.3

243.1

359.2

309.1

399.3

0 50

100

Relative Int. (%)

100

150

200

250 D3CO

Noroxycodone-d3, methoxyimino/ethyl/ trimethylsilyl derivative

50 73.1

300

O

C23H31D3N2O4Si MW: 433.63

350

O–Si(CH3)3

400

228.1

433.3

II-11-R-ii

N –C 2 H 5

H 3CO–N

191.1 199.1

450

362.2

246.2

312.2

418.3 402.3

0 50

100

150

200

250 m/z

300



350

400

450

195


Relative Int. (%)

100

342.2

H3CO

II-11-S-i

Noroxycodone, methoxyimino/ethyl/ t-butyldimethylsilyl derivative

O–C 2 H 5

O

N –Si(CH3)2C(CH3)3

50

C26H40N2O4Si MW: 472.69

H 3CO–N

115.1 166.0

190.1

255.1 283.2

229.1

311.1

0 50

100

150

200

Relative Int. (%)

100

250

350

400

345.2

D3CO

II-11-S-ii

300

O

N –Si(CH3)2C(CH3)3

C26H37D3N2O4Si MW: 475.71

H 3CO–N

115.1 166.1

193.1

232.2

258.1

286.1

500

Noroxycodone-d3, methoxyimino/ethyl/ t-butyldimethylsilyl derivative

O–C 2 H 5

50

450

314.2

0 50

100

150

200

250

300

350

400

450

500


100

Noroxycodone, methoxyimino/acetyl/ trimethylsilyl derivative

50

96.0

II-11-T-i

269.4

281.2

H3CO

O–Si(CH3)3

O

C23H32N2O5Si 181.0 MW: 444.60 153.4

222.2

323.0

N –COCH 3 413.1

444.2

371.0

H 3CO–N


100

100 73.1

150

200

Noroxycodone-d3, methoxyimino/acetyl/ trimethylsilyl derivative

50 89.1

C23H29D3N2O5Si MW: 447.61 164.2

250

300

II-11-T-ii

350

400

D3CO

284.3

O–Si(CH3)3

O

272.3 225.1

450

N –COCH 3

416.4

H 3CO–N

188.2

447.4

374.2

326.4

0 50

Relative Int. (%)

100

100

73.1

150

Noroxycodone, methoxyimino/propionyl/ trimethylsilyl derivative C24H34N2O5Si MW: 458.62

50

200

250 m/z

II-11-U-i

198.0 222.1

269.2

300

281.2

350

H3CO

N –COC 2 H 5

H 3CO–N

328.1

427.2

458.3

371.3 443.3

153.0

115.1

450

O–Si(CH3)3

O

238.2

400

401.3


100

100 73.1

150

Noroxycodone-d3, methoxyimino/propionyl/ trimethylsilyl derivative C24H31D3N2O5Si MW: 461.64

50

200

250

II-11-U-ii

300 272.2

350

284.3 D3CO

H 3CO–N

450

500

O–Si(CH3)3

O

200.9 225.1

400

430.3

N –COC 2 H 5

461.3

374.3 331.2 404.2

446.3

0 50

100

150

200

250

300 m/z



350

400

450

500

196


Relative Int. (%)

100

Noroxycodone, hydroxylimino/di-ethyl/ trimethylsilyl derivative

73.2

50

II-11-V-i

H3CO O

C24H36N2O4Si MW: 444.64 213.3

228.2

243.2

444.3 O–C 2 H 5 N –Si(CH3)3

H 5 C 2 –O–N

429.5 354.3

374.2

399.3

0 50

100

Relative Int. (%)

100

150

200

Noroxycodone-d3, hydroxylimino/di-ethyl/ trimethylsilyl derivative

50

250

300

II-11-V-ii

D3CO O

C24H33D3N2O4Si MW: 447.66

73.2

213.1

231.2

246.1

350

400

450 447.3

O–C 2 H 5 N –Si(CH3)3

H 5 C 2 –O–N

357.8

376.3

432.4

0 50

100

150

200

250 m/z

300



350

400

450

197

Figure II-12. Mass spectra of buprenorphine and its deuterated analogs (buprenorphine-d4): (A) methyl-derivatized; (B) ethyl-derivatized; (C) acetyl-derivatized; (D) MBTFA-derivatized; (E)PFP-derivatized; (F) HFB-derivatized; (G) TMS-derivatized; (H) [TMS]2-derivatized; (I) t-BDMS-derivatized.

Relative Int. (%)

100

H 3C–O

Buprenorphine (CAS NO.52485-79-7), methyl derivative 55.1

50

392.2

O

C30H43NO4 MW: 481.67

-

H3CO HO– C –CH 3

101.2

181.1

100

Relative Int. (%)

100

150

200

250

448.3

366.2

300

350

400

H 3C–O

Buprenorphine-d4 (CAS NO.136781-89-0), methyl derivative

D N C

500

II-12-A-ii

D D D

-


428.3 452.3

370.2

C(CH3)3

101.2

481.3

450

396.2

O

C30H39D4NO4 59.1 MW: 485.69

50

424.3

C(CH3)3

0 50

II-12-A-i

H H N C

485.3

0 50

100

150

200

250

300

350

400

450

500


100

Buprenorphine, ethyl derivative

H 5 C 2 –O

50 55.1

101.1


438.3

150

200

250

300

D N C

O

C31H41D4NO4 MW: 499.72

350

400

450

II-12-B-ii

D D

-

D

442.3


59.1

500

410.3

H 5 C 2 –O

Buprenorphine-d4, ethyl derivative

462.2 495.4

394.3

C(CH3)3

100

50

-


0 100

H H N C

O

C31H45NO4 MW: 495.69

406.2

II-12-B-i

101.2

466.3 499.5

398.2

C(CH3)3

0 50

100

150

200

250

300

350

400

450

500


100

Buprenorphine, acetyl derivative

452.4

-


55.1 101.2

420.3

H H N C

O

C31H43NO5 MW: 509.68

50

II-12-C-i

H 3C–COO

408.3 394.3

C(CH3)3

494.4

509.5

0 50

100

Relative Int. (%)

100

150

Buprenorphine-d4, acetyl derivative

200


150

200

450

250

300 350 m/z Figure II — Opioids

500

550

424.3 456.4

-

C(CH3)3

0

400

D D D D N C


101.2

100

350

II-12-C-ii

O

59.1

50

300

H 3C–COO

C31H39D4NO5 MW: 513.70

50

250

412.4 398.3

498.5

400

450

500

513.5

550

198


Relative Int. (%)

100

F 3C–COO

Buprenorphine, trifluoroacetyl derivative

55.1

50

H H N C

O

C31H40F3NO5 MW: 563.65

-


101.0

474.2

II-12-D-i

506.1 448.2

C(CH3)3

563.3

0 50

100

Relative Int. (%)

100

150

200

250

Buprenorphine-d4, trifluoroacetyl derivative

55.0

300

400

D D D D N C

O

C31H36D4F3NO5 MW: 567.67

50

350

F 3C–COO

500

II-12-D-ii

550

600

478.2

-

510.1


101.0

450

452.0

C(CH3)3

567.1

0 50

100

150

200

250

300

350

400

450

500

550

600


100

F 5 C 2 –COO

Buprenorphine, pentafluoropropionyl derivative

55.1

50

H H N C

O

C32H40F5NO5 MW: 613.66 101.0

524.2

II-12-E-i

-


556.2 512.2 498.2

C(CH3)3

598.3

0 50

100

Relative Int. (%)

100 59.1

50

150

200

250

300

350

F 5 C 2 –COO

Buprenorphine-d4, pentafluoropropionyl derivative

D D D D N C

O

C32H36D4F5NO5 MW: 617.68 101.0

450

100

100 55.1

150

200

250

300

350 m/z

400

650

560.2

450

500

602.4

550

-


617.3

600

650

574.2

II-12-F-i H H N C

O

C33H40F7NO5 MW: 663.66 101.1

50

600

528.2

516.3 502.2

F 7 C 3 –COO

Buprenorphine, heptafluorobutyryl derivative

550

-

C(CH3)3

50

500

II-12-E-ii


0

Relative Int. (%)

400

613.3

606.2 548.2

C(CH3)3

663.4


100

100

150

200

250

Buprenorphine-d4, 59.1 heptafluorobutyryl derivative

300

400

450

F 7 C 3 –COO D D D D N C

O

C33H36D4F7NO5 MW: 667.69 101.1

50

350


500

50

100

150

200

250

300

350

-

400

450


650

700

610.2 552.2

m/z


600 578.2

II-12-F-ii

C(CH3)3

0

550

500

550

667.2

600

650

700

199


Relative Int. (%)

100

(H3C)3Si–O

Buprenorphine, trimethylsilyl derivative 55.0

50

C32H49NO4Si MW: 539.82

73.1

H H N C

O

450.2

II-12-G-i

-


482.2 438.2 424.2

C(CH3)3

506.3 539.3

0 50

100

Relative Int. (%)

100

150

200

250

50

D N C

O

C32H45D4NO4Si MW: 543.85

73.1

350

(H3C)3Si–O

Buprenorphine-d4, trimethylsilyl derivative 59.1

300

400

450

550

454.2

II-12-G-ii

D D

500

D

-


486.3 428.3

C(CH3)3

510.3

442.3

543.2

0 50

100

150

Relative Int. (%)

100

200

250

173.2

300 m/z

(H3C)3SiO

207.0

450

500

555.2 506.4

-

438.3

C35H57NO4Si2 MW: 612.00 596.5

373.9

C(CH3)3

550

Buprenorphine, di-trimethylsilyl derivative

II-12-H-i

H3CO (H3C)3Si–O– C –CH 3

73.1 103.0

400

H H N C

O

50

350

612.1

0 50

100

150

Relative Int. (%)

100

200

250

173.1

300

350

400

(H3C)3SiO D D D D N C

O

50

450

209.0

99.2

550

-

558.3 510.4

C(CH3)3

378.2

350 m/z

400

600

650

Buprenorphine-d4, di-trimethylsilyl derivative

II-12-H-ii


73.1

500

C35H53D4NO4Si2 MW: 616.03

442.4

600.5

616.5

0 50

100

Relative Int. (%)

100

150

200

55.1

300

(H3C)3C(H3C)2Si–O

Buprenorphine, t-butyldimethylsilyl derivative

50

250

500

550

600

650

492.3

II-12-I-i H H N C

O

C35H55NO4Si MW: 581.90

450

-

506.3


480.3

C(CH3)3

524.3 548.3

424.2

581.4

0 50

100

Relative Int. (%)

100

150

200

300

350

(H3C)3C(H3C)2Si–O

Buprenorphine-d4, t-butyldimethylsilyl derivative

50

250

200

250

484.3

300

350 m/z



600

510.3 528.3 552.4 585.4

428.3

0 150

550

496.3

-

C(CH3)3

100

500

D D D D N C


59.1

50

450

II-12-I-ii

O

C35H51D4NO4Si MW: 585.93

400

400

450

500

550

600

200

Figure II-13. Mass spectra of norbuprenorphine and its deuterated analogs (norbuprenorphine-d3): (A) [methyl]2derivatized; (B) [ethyl]2-derivatized; (C) [acetyl]2-derivatized; (D) [MBTFA]2-derivatized; (E) [PFP]2-derivatized; (F) [HFB]2-derivatized; (G) [TMS]2-derivatized; (H) [TMS]3-derivatized; (I) t-BDMS-derivatized.

Relative Int. (%)

100

352.1

H 3C–O

Norbuprenorphine (CAS NO.78715-23-8), di-methyl derivative

II-13-A-i

O

C27H39NO4 MW: 441.60

50


132.1 163.0

384.1

N –CH 3

366.2

310.0 326.2 340.1

C(CH3)3

408.3

441.3

0 50

100

Relative Int. (%)

100

150

200

250

400

450

352.2

II-13-A-ii

O

C27H36D3NO4 MW: 444.62 133.1

350

H 3C–O

Norbuprenorphine-d3, di-methyl derivative

50

300

D3CO HO– C –CH 3

161.1

387.2

N –CH 3

C(CH3)3

308.2

411.3

369.3

325.3 343.1

444.4

0 50

100

150

200

250 m/z

Relative Int. (%)

100

H 5 C 2 –O

Norbuprenorphine, di-ethyl derivative 87.1

50

300

350

400

450

380.2

II-13-B-i

O

C29H43NO4 MW: 469.66


218.1 232.1

N –C 2 H 5

412.2 397.2 347.0 368.2

C(CH3)3

454.4

422.2

469.3

0 50

100

150

200

250

Relative Int. (%)

100

300

400

50

C29H40D3NO4 MW: 472.67


50

100

150

200

250

415.2

N –C 2 H 5

354.1

C(CH3)3

270.4

0

500

II-13-B-ii

O

87.1

450

380.2

H 5 C 2 –O

Norbuprenorphine-d3, di-ethyl derivative

350

300

422.3

371.3

350

457.3

400

450

472.4

500


100

H 3C–COO

Norbuprenorphine, di-acetyl derivative

O

C29H39NO6 MW: 497.62

50 57.2

101.1

440.3

II-13-C-i -


N COCH 3

408.3 366.3

C(CH3)3

123.1

422.3

380.3

482.4

0 50

100

Relative Int. (%)

100

150

200

250

300

101.1

450

550

443.3

-


N COCH 3

C(CH3)3

126.1

500

II-13-C-ii

O

C29H36D3NO6 MW: 500.64 57.1

400

H 3C–COO

Norbuprenorphine-d3, di-acetyl derivative

50

350

408.3 366.2

383.3

425.3

485.4

0 50


100

150

200

250

300 350 m/z Appendix One — Mass Spectra

400

450

500

550

201


Relative Int. (%)

100

F 3C–COO

Norbuprenorphine, di-trifluoroacetyl derivative

548.3

II-13-D-i

516.2

O

C29H33F6NO6 MW: 605.57

50


N –COCF 3

474.2

C(CH3)3

530.2

590.0

0 50

100

150

Relative Int. (%)

100

200

250

300

350

400

500

F 3C–COO

Norbuprenorphine-d3, di-trifluoroacetyl derivative


N –COCF 3

550

600

650

551.2

516.3

II-13-D-ii

O

C29H30D3F6NO6 MW: 608.58

50

450

474.2 533.2

C(CH3)3

593.3

0 50

100

150

200

Relative Int. (%)

100 57.1

250

300

F 5 C 2 –COO

II-13-E-i

O


119.0

223.1

400

450

500

Norbuprenorphine, di-pentafluoropropionyl derivative

101.1

50

350 m/z

N –COC 2 F 5

383.1

C(CH3)3

550

606.0 630.3 690.3

0 50

100

150

200

Relative Int. (%)

100

250

300

350

F 5 C 2 –COO

II-13-E-ii 57.1 101.1


119.0

400

450

500

550

600

Norbuprenorphine-d3, di-pentafluoropropionyl derivative

O

50

N –COC 2 F 5

C(CH3)3

650

Relative Int. (%)

100

100

150

200

250

300

350

400 m/z

608.3 633.2 693.5

O

50

69.0

117.0 169.0


233.1

500

550

600

Norbuprenorphine, di-heptafluorobutyryl derivative

F 7 C 3 –COO

57.1

450

N –COC 3 F 7

650

716.2 674.2 594.1

551.2

700

748.3

730.3 789.9


100

100

150

200

250

300

350

400

F 7 C 3 –COO

57.1 101.1 69.0


169.0

233.0

500

550

600

650

Norbuprenorphine-d3, di-heptafluorobutyryl derivative

O

50

450

N –COC 3 F 7

C(CH3)3

700

750

100

150

200

250

300

350

400

716.3

C33H30D3F14NO6 MW: 808.61 433.0 551.2 594.1

450 m/z



500

550

600

800

850

II-13-F-ii 751.3

674.1 733.3 793.3

0 50

750

II-13-F-i

C33H33F14NO6 MW: 805.60 433.0

C(CH3)3

750

651.3

616.2

C31H30D3F10NO6 MW: 708.60 574.2 383.0 494.1

700

0 50

650

648.3

616.2

C31H33F10NO6 MW: 705.58 574.2 494.0

600

650

700

750

800

850

202


Relative Int. (%)

100

(H3C)3Si–O

73.0

Norbuprenorphine, di-trimethylsilyl derivative

O

50


102.0

N –Si(CH3)3

II-13-G-i

468.2

C31H51NO4Si2 MW: 557.91

500.3

524.3 542.4

456.2 482.2

C(CH3)3

557.3


100

100

150

73.0

200

250

300

350

(H3C)3Si–O


102.0

450

Norbuprenorphine-d3, di-trimethylsilyl derivative

O

50

400

N –Si(CH3)3

500

550

II-13-G-ii

468.2

C31H48D3NO4Si2 MW: 560.93

600

503.3 527.3 545.4 560.3

459.3 485.3

C(CH3)3

0 50

100

150

200

250

300

350

400

450

500

550

600


100

73.1

(H3C)3Si–O

173.2

O

50


102.1

N –Si(CH3)3

C(CH3)3


100

100

150

200

73.1

250

173.1

300

350

400

(H3C)3Si–O

C34H59NO4Si3 572.4 MW: 630.09

524.4

468.3 456.4

482.3

540.4

450

500

550

D3CO (H3C)3Si–O– C –CH 3

102.1

50

100

N –Si(CH3)3

468.2 459.3

C(CH3)3

150

100

II-13-I-i

200

250

300

73.1

400

450

O

550

650

452.3 494.3

C(CH3)3

246.1

600

470.3

-

N H

207.1

650

438.2


101.1

600

C34H56D3NO4Si3 MW: 633.11 527.4 576.0 485.4 542.4 617.4 632.6

500

(H3C)3C(H3C)2Si–O

Norbuprenorphine, t-butyldimethylsilyl derivative C31H49NO4Si MW: 527.81

50

350 m/z

615.0 630.5

Norbuprenorphine-d3, tri-trimethylsilyl derivative

II-13-H-ii

O

50

0

Relative Int. (%)

Norbuprenorphine, tri-trimethylsilyl derivative

II-13-H-i

527.4


100

100

150

II-13-I-ii

200

250

Norbuprenorphine-d3, t-butyldimethylsilyl derivative

73.1 101.1

350

400

550

455.3


497.3

C(CH3)3

246.1

500

473.3

-

N H

207.1

450 438.2

O

C31H46D3NO4Si MW: 530.83

50

300

(H3C)3C(H3C)2Si–O

530.4

0 50

100

150

200

250

300 m/z

350



400

450

500

550

203

Figure II-14. Mass spectra of fentanyl and its deuterated analogs (fentanyl-d5).

Relative Int. (%)

100

245.1

Fentanyl (CAS NO.437-38-7) C22H28N2O MW: 336.47

50

II-14-i

–C 2 H 4 –N

146.1 189.1

57.1

105.0

77.0

50 100

100

150

50

250

300 D

151.1

O

207.1 281.0

100

150

200 m/z



C D

D

D

C 2H 5

0 50

D

N

–C 2 H 4 –N

105.1

82.1

350

II-14-ii 194.1

57.1

336.3

281.0

250.2

Fentanyl-d5 (CAS NO.118357-29-2) C22H23D5N2O MW: 341.50

200

C C 2H 5

202.1

0

Relative Int. (%)

N O

250

300

341.0

350

204

Figure II-15. Mass spectra of norfentanyl and its deuterated analogs (norfentanyl-d5): (A) underivatized; (B) acetylderivatized; (C) TCA-derivatized; (D) TFA-derivatized; (E) PFP-derivatized; (F) HFB-derivatized; (G) 4-CB-derivatized; (H) TMS-derivatized; (I) t-BDMS-derivatized. Relative Int. (%)

100

83.1

50

O

C

C14H20N2O MW: 232.32

175.1

159.1

C 2H 5

120.1

68.1

150.1 203.1

0 50

100

Relative Int. (%)

100

150

83.0 HN

D

C D

D

N O

98.1

68.0

50

D

125.1

C 2H 5

232.2

200

250 Norfentanyl-d5

II-15-A-ii

D

C14H15D5N2O MW: 237.35

180.1 164.1

155.1 208.1

0 50

100


Norfentanyl

II-15-A-i

N

HN

93.1

150 m/z

83.1

200

250

O

125.1

132.1 158.1

H 3 C–C–N

N O

93.1

50

237.2

57.1

C C 2H 5

149.1

Norfentanyl, acetyl derivative

231.2

175.1

C16H22N2O2 MW: 274.36

II-15-B-i 217.1

274.2

0 50

100

Relative Int. (%)

100

83.1

150

200

125.1

D

O

137.1

163.1

O

154.1

57.1

Norfentanyl-d5, acetyl derivative D

C D

236.2

C16H17D5N2O2 MW: 279.39

D

II-15-B-ii

C 2H 5

180.2

300

D

N

H 3 C–C–N

98.1

50

250

222.2

279.2

0 50

100

150

200

250

300


100

191.0

O Cl 3 C–C–N O

50 57.0

93.0

C

C16H19Cl3N2O2 MW: 377.69

C 2H 5

132.0

82.0

Norfentanyl, trichloroacetyl derivative

II-15-C-i

N

158.0

340.0

249.0

342.0

0 50

100

150

Relative Int. (%)

100

200

250

190.9

300 D

O

Cl 3 C–C–N

50

82.0 137.1 57.0

98.1

C D

D

C16H14D5Cl3N2O2 MW: 382.72

D

C 2H 5

163.1

400 Norfentanyl-d5, trichloroacetyl derivative

II-15-C-ii

D

N

O

350

254.0

345.0

347.0

0 50

100

150

200

250 m/z



300

350

400

205


Relative Int. (%)

100

150.1

F 3 C–C–N

N O

50

93.1

132.1

57.1

Norfentanyl, trifluoroacetyl derivative

O

II-15-D-i

C

C16H19F3N2O2 MW: 328.33

C 2H 5

179.1

77.1

272.1

237.1

328.1

0 50

100

150

Relative Int. (%)

100

200

250

300

350

155.1

II-15-D-ii 50

F 3 C–C–N

D

C D

D

N O

98.1

57.1

D

O

180.1

137.1

82.1

Norfentanyl-d5, trifluoroacetyl derivative

D

C16H14D5F3N2O2 MW: 333.36

C 2H 5

277.1

241.1

333.2

0 50

100

150

Relative Int. (%)

100

200 m/z

250

150.1

F 5 C 2 –C–N

N O

57.1

132.1

93.1

C

C17H19F5N2O2 MW: 378.34

C 2H 5

229.1

77.1

350

Norfentanyl, pentafluoropropionyl derivative

O

II-15-E-i 50

300

175.1

287.1

322.1

378.1

0 50

100

150

Relative Int. (%)

100

200

250

300

350

155.1 F 5 C 2 –C–N

50 82.1

98.1

D

C D

D

229.1

137.1

D

N

O

57.1

D

O

II-15-E-ii

Norfentanyl-d5, pentafluoropropionyl derivative C17H14D5F5N2O2 MW: 383.37

C 2H 5

180.1

400

291.1

327.1

383.2

0 50

100

150

200

250

300

350

400


100

150.1 F 7 C 3 –C–N

N O

50 93.1

57.1

Norfentanyl, heptafluorobutyryl derivative

O

II-15-F-i 132.1

C

C18H19F7N2O2 MW: 428.34

279.0

C 2H 5

175.1

372.1

428.1

0 50

100

150

Relative Int. (%)

100

200

250

300

350

D

II-15-F-ii

O

57.1

82.1

137.1

D

N

F 7 C 3 –C–N

50

D

C D

450

Norfentanyl-d5, heptafluorobutyryl derivative

155.1 O

400

D

C18H14D5F7N2O2 MW: 433.37

279.0

C 2H 5

180.1

377.1

433.2

0 50

100

150

200

250 m/z



300

350

400

450

206


Relative Int. (%)

100

II-15-G-i

150.1

H 5C 2OOC(F 2C)3–C–N

N O

50

333.1

C 2H 5

175.1

C21H24F6N2O4 MW: 482.42

C

132.1

82.1

57.1

Norfentanyl, 4-carboethoxyhexafluorobutyryl derivative

O

259.0

437.1

482.2

0 50

100

150

Relative Int. (%)

100

200

250

300

O

D

350

400

155.1

II-15-G-ii

H 5C 2OOC(F 2C)3–C–N O

82.1

57.1

D

C D

137.1

C21H19D5F6N2O4 MW: 487.45

D

333.1

C 2H 5

180.1

500

Norfentanyl-d5, 4-carboethoxyhexafluorobutyryl derivative

D

N

50

450

259.0

442.1

487.2

0 50

100

150

200

250

300

350

400

450

500


100

155.1

II-15-H-i

(H3C)3Si–N

73.1

O

50 128.1 102.1

Norfentanyl, trimethylsilyl derivative

N C

C17H28N2OSi MW: 304.50

247.2

C 2H 5

140.1

206.1

289.2

231.1

304.2

0 50

100

150

Relative Int. (%)

100

200

250

155.1

D

II-15-H-ii

(H3C)3Si–N

73.1

50 128.1

140.1 211.1

82.1

C D

350

Norfentanyl-d5, trimethylsilyl derivative

D D

N

O

300

C17H23D5N2OSi MW: 309.53

252.2

D

C 2H 5

294.2

236.2

309.2

0 50

100

150

200 m/z

Relative Int. (%)

100

250

300

206.1 (H3C)3C(H3C)2Si–N

N O

50

289.2

C

C20H34N2OSi MW: 346.58

73.1

231.1

331.2

0 100

150

200

Relative Int. (%)

100

O

137.1

D

D

C D

D

250

300

211.1 294.2 D

N

(H3C)3C(H3C)2Si–N

50

II-15-I-ii

236.2

150

200

250 m/z



400

Norfentanyl-d5, t-butyldimethylsilyl derivative C20H29D5N2OSi MW: 351.61 336.3

0 100

350

C 2H 5

73.1

50

Norfentanyl, t-butyldimethylsilyl derivative

II-15-I-i

C 2H 5

132.1

50

350

300

350

400

207

Figure II-16. Mass spectra of methadone and its deuterated analogs (methadone-d3, -d9).

Relative Int. (%)

100

72.1

Methadone (CAS NO.76-99-3)

II-16-i

O H 3C

50

H 2C

C

C

CH 2 CH

N

CH 3

C21H27NO MW: 309.45

CH 3 CH 3

294.2 309.1

165.0


100

100

150

200

250

72.1

300

Methadone-d3 (CAS NO.60263-63-0)

II-16-ii

O D 3C

50

H 2C

C

C

CH 2 CH

N

CH 3

C21H24D3NO MW: 312.46

CH 3 CH 3

297.2

165.1


100

350

100

150

200

250

312.2

300

350

78.2 Methadone-d9

II-16-iii

O D 3C

50

H 2C

C

C

CH 2 CH CH 3

N

C21H18D9NO MW: 318.50

CD 3 CD 3

303.2

165.0

0 50

100

150

200 m/z



250

300

318.3

350

208

Figure II-17. Mass spectra of EDDP and its deuterated analogs (EDDP-d3).

Relative Int. (%)

100

2-ethylidine-1,5-dimethyl-3,3diphenylpyrrolidine (CAS NO.32705-91-2)

50

C20H23N MW: 277.40

69.1

H 3C

115.0 91.0

277.1

II-17-i N CH 3

262.1

CH 2CH 3

165.0

200.1

178.0

220.1


100

100

150

200

50

72.1

H 3C

91.0

115.0

300 280.1

2-ethylidine-1,5-dimethyl-3,3diphenylpyrrolidine-d3 C20H20D3N MW: 280.42

250

II-17-ii N CH 3

CH 2CD 3

203.1

165.0

220.1

265.1

178.0

0 50

100

150

200 m/z



250

300

209

Figure II-18. Mass spectra of propoxyphene and its deuterated analogs (propoxyphene-d5, -d7, -d11).

Relative Int. (%)

100

58.1

II-18-i

O

H 3C

50 91.1

H 2C

C

O C

CH

H 2C

CH 3

115.0

N

CH 3

C22H29NO2 MW: 339.47

CH 3

193.1

208.1

250.1


100

100

D

58.1

H 3C

50 91.1


100

D

200

H 2C

C

D O C

D CH

H 2C

CH 3

100

150 D O H 3C

50

N

D 2C

C

D

50

D CH

H 2C

CH 3

D

64.1

D

350

C22H24D5NO2 MW: 344.50

255.2

250

300

350 Propoxyphene-d7

N

CH 3

C22H22D7NO2 MW: 346.51

II-18-iii

CH 3

215.1

200

257.1

250

300

350

D

Propoxyphene-d11 O H 3C

50 91.1

0 100

H 2C

C

D O C

D CH

H 2C

CH 3

N

CD 3 CD 3

150

200 m/z

C22H18D11NO2 MW: 350.54

II-18-iv 213.1

119.1



213.1

200

D O C

150

II-18-ii

CH 3

200.1

100

50

300

D

98.1

100

CH 3

198.1

119.0

58.1

0

250

D

Propoxyphene-d5 (CAS NO.136765-49-6) O

0

Relative Int. (%)

150

Propoxyphene (CAS NO.469-62-5)

261.1

250

300

350

210

Figure II-19. Mass spectra of norpropoxyphene and its deuterated analogs (norpropoxyphene-d5).

Relative Int. (%)

100

44.1

Norpropoxyphene (CAS NO.66796-40-5)

II-19-i 100.1

50 57.1

O H 3C

H 2C

C

234.1 O C H 2C

91.0

CH CH 2 NH

C21H27NO2 MW: 325.44

CH 3

CH 3

281.0

207.0

129.1

307.2


100

90 44.1

D

II-19-ii 100.1

50 57.1

140 O H 3C

H 2C

C

88.1

D

190

240

290

140

D CH

H 2C

CH 3

239.2 CH 2 NH

C21H22D5NO2 MW: 330.47

CH 3

207.0

281.0

190

240 m/z



390

Norpropoxyphene-d5 D O C

129.1

90

340

D

0 40

325.0

290

312.2

327.0

340

390

211

Figure II-20. Mass spectra of meperidine and its deuterated analogs (meperidine-d4).

Relative Int. (%)

100

71.1

CH 3

COCH 2CH 3

50 57.1

247.1 172.1

C15H21NO2 MW: 247.33

218.1

O

103.0

91.0

Meperidine (CAS NO.57-42-1)

II-20-i

N

144.1

190.0

150

200

232.1

0 50

100

Relative Int. (%)

100

73.1

CH 3 D D

50

57.1

105.0 93.0

300

Meperidine-d4 (CAS NO.53484-73-4)

II-20-ii

N D D COCH 2CH 3

250

251.1

C15H17D4NO2 MW: 251.36

222.1

175.1

O

144.1

192.1

234.1

0 50

100

150

200 m/z



250

300

212

Figure II-21. Mass spectra of normeperidine and its deuterated analogs (normeperidine-d4): (A) underivatizedderivatized; (B) ethyl-derivatized; (C) propyl-derivatized; (D) butyl-derivatizedacetyl; (E) acetyl-derivatized; (F) TCA-derivatized; (G) TFA-derivatized; (H) PFP-derivatized; (I) HFB-derivatized; (J) 4-CB-derivatized; (K) TMSderivatized; (L) t-BDMS-derivatized. Relative Int. (%)

100

57.1

H

Normeperidine (CAS NO.77-17-8)

II-21-A-i

C14H19NO2 MW: 233.31

N

COCH 2CH 3

50 91.0

77.0

103.0

233.1

O

158.1 131.0

187.0

204.1


100

100 59.1

150

200 H

Normeperidine-d4 (CAS NO.160227-47-4)

II-21-A-ii

C14H15D4NO2 MW: 237.33

D D

50 133.0

93.0

N

D D COCH 2CH 3

237.1

O

164.1

105.0 79.0

250

208.1

191.1

0 50

Relative Int. (%)

100

100

Normeperidine, ethyl derivative

150 m/z

200

N

C16H23NO2 MW: 261.36

50

246.1

C 2H 5

II-21-B-i

250

COCH 2CH 3

85.1 71.1

O

103.1

261.1

232.1

188.1

158.1


100

100 Normeperidine-d4, ethyl derivative

150

200

II-21-B-ii D

C16H19D4NO2 MW: 265.38

50

D D COCH 2CH 3

71.1

O

105.0

300

250.1

N

D

87.1

250

C 2H 5

265.1

236.1

192.1

161.1

0 50

100

150

200

250

300


100

246.1

Normeperidine, propyl derivative

C 3H 7

II-21-C-i

N

C17H25NO2 MW: 275.39

50

COCH 2CH 3 O

103.0

202.1

275.1


100

100 Normeperidine-d4, propyl derivative

150

250

300

250.1

II-21-C-ii

C 3H 7

C17H21D4NO2 MW: 279.41

50

200

D

N

D

D D COCH 2CH 3 O

0 50

100

150

200 m/z



279.2

206.2

105.1

250

300

213


Relative Int. (%)

100

Normeperidine, butyl derivative

C 4H 9

C18H27NO2 MW: 289.41

50

246.1

II-21-D-i

N COCH 2CH 3 O

216.1

289.2


100

100

150

Normeperidine-d4, butyl derivative

C 4H 9

250

300

250.2

II-21-D-ii

N

D

C18H23D4NO2 MW: 293.44

50

200

D D COCH 2CH 3

D

O

220.2

293.2

0 50

100

150

200

250

300


100

187.1

COCH 3 N

50

C16H21NO3 MW: 275.34

COCH 2CH 3

158.1

O

57.1

Normeperidine, acetyl derivative

II-21-E-i 232.1

202.1

275.1

103.1

91.1

0 50

100

Relative Int. (%)

100

150

200

COCH 3

D

D D COCH 2CH 3

50

236.2

C16H17D4NO3 MW: 279.36 279.2

105.1

93.1

0

206.2

161.1

O

59.1

300 Normeperidine-d4, acetyl derivative

II-21-E-ii

N

D

50

250

191.1

100

150

200

250

300


100

COCH 2CH 3

143.0 103.0

II-21-F-i

N

C16H18Cl3NO3 MW: 378.68

50

342.0

COCCl 3

Normeperidine, trichloroacetyl derivative

117.0

O

158.0

268.0

232.1 304.0


100

100

150

200 COCCl 3

Normeperidine-d4, trichloroacetyl derivative D

119.0

350

400

346.1

D D COCH 2CH 3

236.1

O

146.0 105.0

300

II-21-F-ii

N

D

C16H14D4Cl3NO3 MW: 382.70

50

250

271.0

161.1

308.0

0 50

100

150

200

250 m/z



300

350

400

214


Relative Int. (%)

100

Normeperidine, trifluoroacetyl derivative

91.1

256.1

COCH 2CH 3

103.1

II-21-G-i

N

C16H18F3NO3 MW: 329.31

50

241.1

COCF 3

143.1

329.1

O

117.1


100

100

150

200

Normeperidine-d4, trifluoroacetyl derivative D

146.1

D

105.1 93.1

300

350

243.1

COCF 3

C16H14D4F3NO3 MW: 333.34

50

250

II-21-G-ii

N D D COCH 2CH 3

259.1 333.1

O

119.1

0 50

Relative Int. (%)

100

100

150

Normeperidine, pentafluoropropionyl derivative C17H18F5NO3 MW: 379.32 103.1

50

200 m/z

250

300

350

291.1

COC 2 F 5

II-21-H-i

N

143.1

306.1

COCH 2CH 3

379.1

O

117.1

176.0

202.0

360.1


100

100

150

200

250

Normeperidine-d4, pentafluoropropionyl derivative

D

350

II-21-H-ii

N D D COCH 2CH 3

D

119.1

400

293.1

COC 2 F 5

146.1

C17H14D4F5NO3 MW: 383.35 105.1

50

300

310.1

383.1

O

177.0

203.0

364.1

0 50

100

150

200

250

300

350

400


100

Normeperidine, heptafluorobutyryl derivative C18H18F7NO3 MW: 429.33 103.1

50

341.1

COC 3 F 7

II-21-I-i

N

143.1 356.1

COCH 2CH 3

429.1

O

117.1

169.0

226.0


100

100

150

200

250

Normeperidine-d4, heptafluorobutyryl derivative

D

105.1

146.1

D

350

400

N

II-21-I-ii

D D COCH 2CH 3

360.1 433.1

O

119.1

169.0

450

343.1

COC 3 F 7

C18H14D4F7NO3 MW: 433.35

50

300

227.0

0 50

100

150

200

250 m/z



300

350

400

450

215


Relative Int. (%)

100

Normeperidine, 4-carboethoxyhexafluorobutyryl derivative

50

II-21-J-i

N

143.1

C21H23F6NO5 MW: 483.40 103.1

395.1

CO(CF2)3COOC2H 5

COCH 2CH 3

410.1

O

232.1

483.1 438.1

195.0


100

100

150

200

250

300

Normeperidine-d4, 4-carboethoxyhexafluorobutyryl derivative C21H19D4F6NO5 MW: 487.43 105.1

50

350

400

146.1

II-21-J-ii

N D D COCH 2CH 3

D

414.1

O

236.2

500

397.1

CO(CF2)3COOC2H 5 D

450

487.2 442.1

195.0

0 50

100

150

200

250

300

350

400

450

500


100

73.1 Si(CH ) 33

129.1

Normeperidine, trimethylsilyl derivative

N

50

COCH 2CH 3

154.1

O

59.1

290.1

230.1

C17H27NO2Si MW: 305.49

304.2

276.1

198.1

II-21-K-i

248.1

0 50

100

Relative Int. (%)

100

150

73.1 Si(CH3)3 D

D D COCH 2CH 3

D

50

131.1

N

158.1

O

200

250

300

Normeperidine-d4, trimethylsilyl derivative C17H23D4NO2Si MW: 309.51

59.1

350 308.2

280.2 236.2

II-21-K-ii

294.2 250.1

202.1

0 50

100

150

200 m/z

Relative Int. (%)

100

II-21-L-i 50

250

290.2

Si(CH3)2C(CH3)3

132.1

300

N

350

Normeperidine, t-butyldimethylsilyl derivative C20H33NO2Si MW: 347.57

COCH 2CH 3

103.1

O

73.1

262.2

216.1

175.1

332.2 347.3


100

100

150

200

300 294.2

Si(CH3)2C(CH3)3

II-21-L-ii D

133.1

50

250

N

D

103.1

D D COCH 2CH 3

219.1

179.1

400

Normeperidine-d4, t-butyldimethylsilyl derivative C20H29D4NO2Si MW: 351.59

266.2

O

73.1

350

336.2 351.3

0 50

100

150

200

250 m/z



300

350

400

217

Summary of Drugs, Isotopic Analogs, and Chemical Derivatization Groups Included in Figure III (Hallucinogens) Compound

Isotopic analog


Figure #

Cannabinol

d3

Methyl, ethyl, propyl, butyl, propionyl (10)

III-1

Tetrahydrocannabinol

d3

Methyl, ethyl, propyl, butyl, TFA, propionyl, PFP, HFB, TMS, t-BDMS (20)

III-2

THC-OH

d3

[Methyl]2, [ethyl]2, [propyl]2, [butyl]2, [TFA]2, propionyl, [PFP]2, [HFB]2, [TMS]2, [t-BDMS]2 (20)

III-3

THC-COOH

d 3, d 9

[Methyl]2, [ethyl]2, [propyl]2, [butyl]2, propionyl, [TMS]2, [t-BDMS]2, methyl/TFA, PFPoxy/PFP, HFPoxy/HFB (30)

III-4

Ketamine

d4

None, acetyl, TFA, HFB, PFB, TMS (12)

III-5

Norketamine

d4

None, acetyl, TCA, TFA, PFP, HFB, 4-CB, PFB, TMS, TFA/t-BDMS, PFP/t-BDMS, HFB/t-BDMS (24)

III-6

Phencyclidine

d5

None (2)

III-7

LSD

d3

None, TMS (4)

III-8

Mescaline

d9

Acetyl, TCA, TFA, PFP, HFB, 4-CB, [TMS]2, t-BDMS, TFA/TMS, TFA/t-BDMS, PFP/TMS, PFP/t-BDMS, HFB/TMS, HFB/t-BDMS (28)

III-9

Psilocin

d10

None, acetyl, [acetyl]2, [TMS]2, t-BDMS, [t-BDMS]2 (12) Total no. of mass spectra: 162

Figure III — Hallucinogens


III-10

219

Appendix One — Figure III Mass Spectra of Commonly Abused Drugs and Their Isotopically Labeled Analogs in Various Derivatization Forms — Hallucinogens Figure III-1. Mass spectra of cannabinol and its deuterated analogs (cannabinol-d3): (A) methyl-derivatized; (B) ethylderivatized; (C) propyl-derivatized; (D) butyl-derivatized; (E) propionyl-derivatized ............................................................... 220 Figure III-2. Mass spectra of tetrahydrocannabinol and its deuterated analogs (tetrahydrocannabinol-d3): (A) methylderivatized; (B) ethyl-derivatized; (C) propyl-derivatized; (D) butyl-derivatized; (E) TFA-derivatized; (F) propionylderivatized; (G) PFP-derivatized; (H) HFB-derivatized; (I) TMS-derivatized; (J) t-BDMS-derivatized ................................... 222 Figure III-3. Mass spectra of THC-OH and its deuterated analogs (THC-OH-d3): (A) [methyl]2-derivatized; (B) [ethyl]2derivatized; (C) [propyl]2-derivatized; (D) [butyl]2-derivatized; (E) [TFA]2-derivatized; (F) propionyl-derivatized; (G) [PFP]2-derivatized; (H) [HFB]2-derivatized; (I) [TMS]2-derivatized; (J) [t-BDMS]2-derivatized ............................................. 226 Figure III-4. Mass spectra of THC-COOH and its deuterated analogs (THC-COOH-d3, -d9): (A) [methyl]2-derivatized; (B) [ethyl]2-derivatized; (C) [propyl]2-derivatized; (D) [butyl]2-derivatized; (E) propionyl-derivatized; (F) [TMS]2derivatized; (G) [t-BDMS]2-derivatized; (H) methyl/TFA-derivatized; (I) PFPoxy/PFP-derivatized; (J) HFPoxy/HFBderivatized ..................................................................................................................................................................................... 230 Figure III-5. Mass spectra of ketamine and its deuterated analogs (ketamine-d4): (A) underivatized; (B) acetyl-derivatized; (C) TFA-derivatized; (D) HFB-derivatized; (E) PFB-derivatized; (F) TMS-derivatized ........................................................... 235 Figure III-6. Mass spectra of norketamine and its deuterated analogs (norketamine-d4): (A) underivatized; (B) acetylderivatized; (C) TCA-derivatized; (D) TFA-derivatized; (E) PFP-derivatized; (F) HFB-derivatized; (G) 4-CB-derivatized; (H) PFB-derivatized; (I) TMS-derivatized; (J) TFA/t-BDMS-derivatized; (K) PFP/t-BDMS-derivatized; (L) HFB/tBDMS-derivatized ........................................................................................................................................................................ 237 Figure III-7. Mass spectra of phencyclidine and its deuterated analogs (phencyclidine-d5) ..................................................... 241 Figure III-8. Mass spectra of LSD and its deuterated analogs (LSD-d3): (A) underivatized-derivatized; (B) TMSderivatized ..................................................................................................................................................................................... 242 Figure III-9. Mass spectra of mescaline and its deuterated analogs (mescaline-d9): (A) acetyl-derivatized; (B) TCAderivatized; (C) TFA-derivatized; (D) PFP-derivatized; (E) HFB-derivatized; (F) 4-CB-derivatized; (G) [TMS]2-derivatized; (H) t-BDMS-derivatized; (I) TFA/TMS-derivatized; (J) TFA/t-BDMS-derivatized; (K) PFP/TMS-derivatized; (L) PFP/tBDMS-derivatized; (M) HFB/TMS-derivatized; (N) HFB/t-BDMS-derivatized ....................................................................... 243 Figure III-10. Mass spectra of psilocin and its deuterated analogs (psilocin-d10): (A) underivatized; (B) acetyl-derivatized; (C) [acetyl]2-derivatized; (D) [TMS]2-derivatized; (E) t-BDMS-derivatized; (F) [t-BDMS]2-derivatized ................................ 248



220

Figure III-1. Mass spectra of cannabinol and its deuterated analogs (cannabinol-d3): (A) methyl-derivatized; (B) ethyl-derivatized; (C) propyl-derivatized; (D) butyl-derivatized; (E) propionyl-derivatized.

Relative Int. (%)

100

Cannabinol (CAS NO.521-35-7), methyl derivative C22H28O2 MW: 324.46

50

309.1

CH 3

III-1-A-i

OCH3 H C O 3 H C 3

CH (CH ) CH 2 23 3

209.1

238.1

324.2

252.1


100

100

150

Cannabinol-d3, methyl derivative

250

350

III-1-A-ii

OCH3 H C O 3 H C 3

300 312.2

CH 3

C22H25D3O2 MW: 327.47

50

200

CH (CH ) CD 2 23 3

209.0

238.0

327.2

252.1

0 50

Relative Int. (%)

100

100

150

Cannabinol, ethyl derivative

250

300

H C O 3 H C 3

CH (CH ) CH 2 23 3

338.2 295.1


100

150

Cannabinol-d3, ethyl derivative

200

250

300

OC 2H 5 H C O 3 H C 3

CH (CH ) CD 2 23 3

341.2

238.1 298.1

0 50


350 326.2

III-1-B-ii

CH 3

C23H27D3O2 MW: 341.50

50

323.1

OC 2H 5

238.0

100

350

III-1-B-i

CH 3

C23H30O2 MW: 338.48

50

200 m/z

100

150

Cannabinol, propyl derivative

250

350

III-1-C-i

OC 3H 7 H C O 3 H C 3

300

337.2

CH 3

C24H32O2 MW: 352.51

50

200 m/z

CH (CH ) CH 2 23 3

238.0

352.2

295.1


100

100

150

Cannabinol-d3, propyl derivative

250

OC 3H 7 H C O 3 H C 3

300

III-1-C-ii

CH 3

C24H29D3O2 MW: 355.53

50

200

350

400

340.2

CH (CH ) CD 2 23 3

238.1

355.2

298.2

0 50

100

150

200

250 m/z



300

350

400

221

Figure III-1. (Continued)

Relative Int. (%)

100

Cannabinol, butyl derivative C25H34O2 MW: 366.54

50

351.2

CH 3

III-1-D-i

OC 4H 9 H C O 3 H C 3

CH (CH ) CH 2 23 3

238.0

366.2

295.1


100

100

150

Cannabinol-d3, butyl derivative C25H31D3O2 MW: 369.56

50

200

250

350

400 354.2

CH 3

III-1-D-ii

OC 4H 9 H C O 3 H C 3

300

CH (CH ) CD 2 23 3

238.0

369.2

298.1

0 50

100

150

200

250

300

350

400


100

Cannabinol, propionyl derivative C24H30O3 MW: 366.49

50

III-1-E-i

CH 3

295.1

H C O 3 H C 3

CH (CH ) CH 2 23 3

366.2

238.0 251.1

310.1


100

100

150

Cannabinol-d3, propionyl derivative C24H27D3O3 MW: 369.51

50

200

250

100

150

400 354.2

CH (CH ) CD 2 23 3

369.2

238.0 251.1

200

250 m/z



350

III-1-E-ii

OCOC 2H 5 H C O 3 H C 3

300 298.1

CH 3

313.2

0 50

351.1

OCOC 2H 5

300

350

400

222

Figure III-2. Mass spectra of tetrahydrocannabinol and its deuterated analogs (tetrahydrocannabinol-d3): (A) methylderivatized; (B) ethyl-derivatized; (C) propyl-derivatized; (D) butyl-derivatized; (E) TFA-derivatized; (F) propionylderivatized; (G) PFP-derivatized; (H) HFB-derivatized; (I) TMS-derivatized; (J) t-BDMS-derivatized. Relative Int. (%)

100

Tetrahydrocannabinol (CAS

CH

NO.5957-75-5),

328.2

OCH3

methyl derivative C22H32O2 MW: 328.49

50

313.2

III-2-A-i

3

245.1

H C 3 H C O 3

CH (CH ) CH 2 23 3

257.1

271.2

207.1

81.1

285.2 297.2


100

100 Tetrahydrocannabinol-d3 (CAS NO.81586-39-2), methyl derivative

200 CH

250

H C 3 H C O 3

100

150

97.1

300.2

250

300

III-2-B-i

3

350

342.3

327.2

OC 2H 5

C23H34O2 MW: 342.51

50 57.1

CH

288.2

272.2

200 m/z

Tetrahydrocannabinol, ethyl derivative

331.3

257.2 210.1

100

350 316.2

248.2

CH (CH ) CD 2 23 3

81.1

50

300

III-2-A-ii

3 OCH3

C22H29D3O2 MW: 331.51

50

0

Relative Int. (%)

150

H C 3 H C O 3

111.1

CH (CH ) CH 2 23 3

231.1

174.1

259.2 313.2 271.2 299.2 286.2

0 50

100

Relative Int. (%)

100

150

200

Tetrahydrocannabinol-d3, ethyl derivative

50

57.1

C23H31D3O2 MW: 345.53

97.1

CH

250

350

OC 2H 5

CH (CH ) CD 262.2 2 23 3

316.2

302.2 271.2 286.2

111.1 234.2

174.1

400

345.3

330.3

III-2-B-ii

3

H C 3 H C O 3

300

0 50

100

150

200

250

300

350

400


100

Tetrahydrocannabinol, propyl derivative

CH

OC 3H 7

C24H36O2 MW: 356.54

50

57.1

81.1

H C 3 H C O 3

CH (CH ) CH 2 23 3

273.2

356.3

341.3

III-2-C-i

3

313.2

285.2 297.2

231.1

149.0


100

100

150

200

Tetrahydrocannabinol-d3, propyl derivative

CH

57.1

81.1

300

H C 3 H C O 3

350

400 359.3

344.3

III-2-C-ii

3

316.2

OC 3H 7

C24H33D3O2 MW: 359.56

50

250

CH (CH ) CD 2 23 3

276.2

300.2 285.2

234.2

149.0

0 50

100

150

200

250 m/z



300

350

400

223


Relative Int. (%)

100

Tetrahydrocannabinol, butyl derivative

CH

OC 4H 9

C25H38O2 MW: 370.57

50

370.3

355.2

III-2-D-i

3

H C 3 H C O 3

313.2

CH (CH ) CH 2 23 3

299.1

287.2

327.2

231.1

81.1

0 50

100

Relative Int. (%)

100

150

Tetrahydrocannabinol-d3, butyl derivative C25H35D3O2 MW: 373.59

50

200 CH

250

300

350 358.2

III-2-D-ii

3 OC 4H 9

H C 3 H C O 3

CH (CH ) CD 2 23 3

373.3

316.2 300.2

290.2

330.2

234.1

81.1

400

0 50

100

150

200

250

300

350

400


100

Tetrahydrocannabinol, trifluoroacetyl derivative C23H29F3O3 MW: 410.47

50

69.1

CH

OCOCF3 H C 3 H C O 3

128.1

410.3

367.2 395.2

339.2

297.2

III-2-E-i

3

327.2

CH (CH ) CH 2 23 3

313.2

229.2

165.1

0 50

100

Relative Int. (%)

100

150

200

Tetrahydrocannabinol-d3, trifluoroacetyl derivative C23H26D3F3O3 MW: 413.49

50

69.1

CH

3

300

III-2-E-ii


128.1

250

350

300.3

400

339.1

450 413.3

370.2 398.2

330.2

CH (CH ) CD 2 23 3

316.2

232.2

165.1

0 50

100

Relative Int. (%)

100

150

200

Tetrahydrocannabinol, propionyl derivative

CH

350

400

450

297.2

H C 3 H C O 3

57.1

300

III-2-F-i

3 OCOC 2H 5

C24H34O3 MW: 370.52

50

250 m/z

313.2

CH (CH ) CH 2 23 3

231.1

149.0

243.1

271.1

370.2

0 50

100

Relative Int. (%)

100

150

Tetrahydrocannabinol-d3, propionyl derivative

CH

H C 3 H C O 3

300

III-2-F-ii

3

350

400

300.2

316.2 CH (CH ) CD 2 23 3

149.0

57.1

250

OCOC 2H 5

C24H31D3O3 MW: 373.54

50

200

234.1

243.1

274.1

373.2

0 50

100

150

200

250 m/z



300

350

400

224


Relative Int. (%)

100

Tetrahydrocannabinol, pentafluoropropionyl derivative

CH

III-2-G-i

OCOC 2F 5 H C 3 H C O 3

C24H29F5O3 MW: 460.48

50

119.0

71.1

377.1 3

460.2 392.2 445.2

335.1

229.2

174.1

417.2

CH (CH ) CH 2 23 3

0 50

100

Relative Int. (%)

100

150

200

Tetrahydrocannabinol-d3, pentafluoropropionyl derivative

250

350

450

500

380.2 OCOC 2F 5

463.3 420.2

CH (CH ) CD 2 23 3

395.2 448.2

335.1

232.2

174.1

400

3

H C 3 H C O 3

119.1

74.1

CH

III-2-G-ii

C24H26D3F5O3 MW: 463.50

50

300

0 50

100

150

200

250

300

350

400

450

500


100

Tetrahydrocannabinol, heptafluorobutyryl derivative

50

69.1

297.2

III-2-H-i

3 OCOC 3F 7

H C

C25H29F7O3 MW: 510.48 95.1

CH

169.0 H3 C O 3

467.2 495.2

510.3

427.1

CH (CH ) CH 2 23 3

313.2

229.2

128.1

439.1

453.2 482.2

413.1

0 50

100

Relative Int. (%)

100

150

200

Tetrahydrocannabinol-d3, heptafluorobutyryl derivative

50

69.1

250

CH

300

3 OCOC 3F 7

C25H26D3F7O3 169.0 H 3C O H C 3 MW: 513.50 91.1 128.1

350

300.2

CH (CH ) CD 2 23 3

400

III-2-H-ii

450 439.1

470.2

500

550 513.3

498.2

430.2 316.2

232.2

416.1

456.1 485.2

0 50

Relative Int. (%)

100

100

150

200

Tetrahydrocannabinol, trimethylsilyl derivative

300 m/z CH

350

H C 3 H C O 3

73.1

400

450

CH (CH ) CH 2 23 3

303.2

500

371.3

III-2-I-i

3 OSi(CH3)3

C24H38O2Si MW: 386.64

50

250

550 386.3

315.2 330.2

343.2


100

100

150

Tetrahydrocannabinol-d3, trimethylsilyl derivative C24H35D3O2Si MW: 389.66 73.1

50

200 CH

250

300

350 374.3

III-2-I-ii

3

400 389.3

OSi(CH3)3 H C 3 H C O 3

CH (CH ) CD 2 23 3

306.2

315.2 330.2

346.3

0 50

100

150

200

250 m/z



300

350

400

225


Relative Int. (%)

100

Tetrahydrocannabinol, t-butyldimethylsilyl derivative

50

CH

371.3

III-2-J-i

3 OSi(CH3)2C(CH3)3

428.4

H C 3 H C O 3

C27H44O2Si MW: 428.72 73.1

CH (CH ) CH 2 23 3

249.1

357.3 289.2

345.3

413.3


100

100

150

Tetrahydrocannabinol-d3, t-butyldimethylsilyl derivative

50

200 CH

300

350

400

OSi(CH3)2C(CH3)3

431.4

CH (CH ) CD 2 23 3

252.2

450

374.3

III-2-J-ii

3

H C 3 H C O 3

C27H41D3O2Si MW: 431.74 73.1

250

357.3 292.2

416.4

348.3

0 50

100

150

200

250 m/z



300

350

400

450

226

Figure III-3. Mass spectra of THC-OH and its deuterated analogs (THC-OH-d3): (A) [methyl]2-derivatized; (B) [ethyl]2-derivatized; (C) [propyl]2-derivatized; (D) [butyl]2-derivatized; (E) [TFA]2-derivatized; (F) propionyl-derivatized; (G) [PFP]2-derivatized; (H) [HFB]2-derivatized; (I) [TMS]2-derivatized; (J) [t-BDMS]2-derivatized. Relative Int. (%)

100

THC-OH (CAS NO.36557-05-8), di-methyl derivative C23H34O3 MW: 358.51

50

H C 3 H C O 3

314.2

III-3-A-i

271.2

CH (CH ) CH 2 23 3

174.0

91.1

299.2

231.1

CH OCH 3 2 OCH3

243.1

201.1

356.2


100

100

150

250

CH OCH 3 2 OCH3

THC-OH-d3, di-methyl derivative C23H31D3O3 MW: 361.53

50

200

H C 3 H C O 3

350

302.2

234.1

317.2

400

III-3-A-ii

274.2

CH (CH ) CD 2 23 3

174.1

91.1

300

243.1

196.1

359.2

0 50

100

150

200

250

300

350

400


100

THC-OH, di-ethyl derivative C25H38O3 MW: 386.56

50

H C 3 H C O 3

337.1

III-3-B-i

CH OC 2H 5 2 OC 2H 5 CH (CH ) CH 2 23 3

252.0

71.1

352.2

309.1


100

100

150

THC-OH-d3, di-ethyl derivative C25H35D3O3 MW: 389.58

50

200

250

300

400

340.1

III-3-B-ii

CH OC 2H 5 2 OC 2H 5 H C 3 H C O 3

350

CH (CH ) CD 2 23 3

252.0

71.1

355.1

312.1

0 50

100

150

200

250

300

350

400


100

H C 3 H C O 3

50

351.1

III-3-C-i

CH OC 3H 7 2 OC 3H 7

THC-OH, di-propyl derivative C27H42O3 MW: 414.62

CH (CH ) CH 2 23 3

309.0

252.0

366.2

0 50

100

150

200

250

Relative Int. (%)

100

H C 3 H C O 3

350

400 354.2

III-3-C-ii


50

300

450

THC-OH-d3, di-propyl derivative C27H39D3O3 MW: 417.64

CH (CH ) CD 2 23 3

369.2

312.1

252.0

0 50

100

150

200

250 m/z

300



350

400

450

227


Relative Int. (%)

100

THC-OH, di-butyl derivative C29H46O3 MW: 442.67

50

365.1

CH OC 4H 9 2 OC 4H 9 H C 3 H C O 3

III-3-D-i

CH (CH ) CH 2 23 3

309.1

380.2

252.0

407.3 429.1


100

100

150

200

THC-OH-d3, di-butyl derivative

300

H C 3 H C O 3

350

400

450

368.2


C29H43D3O3 MW: 445.69

50

250

III-3-D-ii

CH (CH ) CD 2 23 3

383.2

312.1

252.0

410.2

0 50

Relative Int. (%)

100

100

150

200

THC-OH, di-trifluoroacetyl derivative

CH OCOCF 3 2 OCOCF3

C25H28F6O5 MW: 522.47

50

250 m/z

H C 3 H C O 3

69.1

300

350

450

408.2

III-3-E-i 365.2

CH (CH ) CH 2 23 3

227.2

400

393.2

313.1

522.2

451.2


100

100

150

200

300

350

400

450

500

550

411.2

THC-OH-d3, di-trifluoroacetyl derivative

CH OCOCF 3 2 OCOCF3

C25H25D3F6O5 MW: 525.49

50

250

H C 3 H C O 3

69.1

III-3-E-ii 368.2

CH (CH ) CD 2 23 3

316.1

230.2

396.2

525.3

451.1

0 50

Relative Int. (%)

100

100

150

200

THC-OH, propionyl derivative

300 m/z

H C 3 H C O 3

350

400

368.2 269.1

Relative Int. (%)

100

150

297.1

353.2

200

250

300

CH OH 2 OCOC 2H 5

C24H31D3O4 MW: 389.54

H C 3 H C O 3

272.1

150

200

250 m/z



400

371.2

CH (CH ) CD 2 23 3

57.0

100

350

III-3-F-ii 300.1

0 50

385.2

315.2

THC-OH-d3, propionyl derivative

50

550

CH (CH ) CH 2 23 3

57.0

100

500

III-3-F-i

0 50

450

312.2

CH OH 2 OCOC 2H 5

C24H34O4 MW: 386.52

50

250

300

356.2

350

388.2

400

228


Relative Int. (%)

100

H C 3 H C O 3

50 119.0

69.1

458.2

CH OCOC 2F 5 2 OCOC 2F 5

III-3-G-i

CH (CH ) CH 2 23 3

THC-OH, di-pentafluoropropionyl derivative C27H28F10O5 MW: 622.49

415.2 363.1

227.1

622.2

551.1

0 50

100

150

200

250

Relative Int. (%)

100

350

400

450

H C 3 H C O 3

50 119.0

500

550

461.3


III-3-G-ii

69.1

300

CH (CH ) CD 2 23 3

650

THC-OH-d3, di-pentafluoropropionyl derivative C27H25D3F10O5 MW: 625.51

418.2 366.1

230.2

600

625.3

551.1

0 50

100

150

200

250

Relative Int. (%)

100

300

350 m/z

400

450

H C 3 H C O 3

50

550

CH (CH ) CH 2 23 3

600

C29H28F14O5 MW: 722.50

465.2

169.0

69.1

227.1

650

THC-OH, di-heptafluorobutyryl derivative

508.2


III-3-H-i

500

722.3

413.1

0 50

100

150

200

250

Relative Int. (%)

100

300

400

450

500

H C 3 H C O 3

50 169.0

550

600

511.3


III-3-H-ii 69.1

350

CH (CH ) CD 2 23 3

650

700

THC-OH-d3, di-heptafluorobutyryl derivative C29H25D3F14O5 MW: 725.52

468.2

725.3

416.1

230.2

750

0 50

100

150

200

250

300

350

400 m/z

450

500

Relative Int. (%)

100

50

H C 3 H C O 3

600

371.3

CH OSi(CH3)3 2 OSi(CH3)3

III-3-I-i

550

700

C27H46O3Si2 MW: 474.82

73.1 459.3

50

100

150

100

200

250

300

350

H C 3 H C O 3

50

400 374.3

CH OSi(CH3)3 2 OSi(CH3)3

III-3-I-ii

73.1

100

150

200

250

500

THC-OH-d3, di-trimethylsilyl derivative

462.3

300 m/z



450

474.3

C27H43D3O3Si2 MW: 477.84

CH (CH ) CD 2 23 3

0 50

750

THC-OH, di-trimethylsilyl derivative

CH (CH ) CH 2 23 3

0

Relative Int. (%)

650

350

400

450

477.4

500

229


Relative Int. (%)

100

413.3

CH OSi(CH3)2C(CH3)3 2 OSi(CH3)2C(CH3)3

III-3-J-i

H C 3 H C O 3

50

THC-OH, di-t-butyldimethylsilyl derivative C33H58O3Si2 MW: 558.98

CH (CH ) CH 2 23 3

73.1

369.3

558.5

0 50

100

150

200

Relative Int. (%)

100

250

300

350

400

CH OSi(CH3)2C(CH3)3 2 OSi(CH3)2C(CH3)3

III-3-J-ii

H C 3 H C O 3

50

450 416.4

500

550

THC-OH-d3, di-t-butyldimethylsilyl derivative C33H55D3O3Si2 MW: 562.00

CH (CH ) CD 2 23 3

73.1

372.3

561.5

0 50

100

150

200

250

300

350 m/z



600

400

450

500

550

600

230

Figure III-4. Mass spectra of THC-COOH and its deuterated analogs (THC-COOH-d3, -d9): (A) [methyl]2-derivatized; (B) [ethyl]2-derivatized; (C) [propyl]2-derivatized; (D) [butyl]2-derivatized; (E) propionyl-derivatized; (F) [TMS]2derivatized; (G) [t-BDMS]2-derivatized; (H) methyl/TFA-derivatized; (I) PFPoxy/PFP-derivatized; (J) HFPoxy/HFBderivatized.

Relative Int. (%)

100

Carboxytetrahydrocannabinol (CAS NO.104874-50-2), di-methyl derivative

50

OCH3 H C 3 H C O 3

C23H32O4 MW: 372.50

313.2

III-4-A-i

COOCH3

357.2

CH (CH ) CH 2 23 3

207.1

372.2 245.1

341.2


100

50

100

150

200

Carboxytetrahydrocannabinol-d3 (CAS NO.136844-96-7), di-methyl derivative

COOCH3

C23H29D3O4 MW: 375.52

250

300

350 316.2

III-4-A-ii

OCH3 H C 3 H C O 3

400

360.2

CH (CH ) CD 2 23 3

210.1

375.3 248.1

344.2


100

100

150

200

Carboxytetrahydrocannabinol-d9, di-methyl derivative

COOCH3

C23H23D9O4 MW: 381.55

50

250

300

350

400

322.3

III-4-A-iii

OCH3 D C 3 D C O 3

363.2

CH (CH ) CD 2 23 3

213.1

381.3

234.1

350.3

0 50

100

150

200

250

300

350

400


100

Carboxytetrahydrocannabinol, di-ethyl derivative

III-4-B-i

OC 2H 5

C25H36O4 MW: 400.55

50

327.2 COOC 2H 5

H C 3 H C O 3

CH (CH ) CH 2 23 3

69.1

371.2

385.3 400.3

355.2

245.1


100

100

150

Carboxytetrahydrocannabinol-d3, di-ethyl derivative C25H33D3O4 MW: 403.57

50

200

250

300

450

III-4-B-ii

OC 2H 5

CH (CH ) CD 2 23 3

69.1

400

330.3

COOC 2H 5

H C 3 H C O 3

350

374.2

388.3 403.3

358.2

248.1


100

100

150

Carboxytetrahydrocannabinol-d9, di-ethyl derivative C25H27D9O4 MW: 409.61

50

200

250

III-4-B-iii

COOC 2H 5 OC 2H 5 D C 3 D C O 3

300

350

400

336.3

CH (CH ) CD 2 23 3

380.3

248.1

450

391.3 409.3

364.2

0 50

100

150

200

250 m/z



300

350

400

450

231


Relative Int. (%)

100

341.3

Carboxytetrahydrocannabinol, di-propyl derivative C27H40O4 MW: 428.60

50

57.1

COOC 3H 7

III-4-C-i

OC 3H 7 H C 3 H C O 3

CH (CH ) CH 2 23 3

385.2

149.0

97.1

413.3 428.3

369.3

283.1


100

100

150

200

Carboxytetrahydrocannabinol-d3, di-propyl derivative C27H37D3O4 MW: 431.62

50

57.1

300

350

400

450

344.3

COOC 3H 7

III-4-C-ii

OC 3H 7 H C 3 H C O 3

97.1

250

CH (CH ) CD 2 23 3

388.3

149.0

416.3

431.3

372.3

286.2


100

100

150

200

Carboxytetrahydrocannabinol-d9, di-propyl derivative C27H31D9O4 MW: 437.66

50

250

300

400

450

350.3

COOC 3H 7

III-4-C-iii

OC 3H 7 D C 3 D C O 3

350

CH (CH ) CD 2 23 3

394.3

419.3 437.4

378.3

289.2

0 50

Relative Int. (%)

100

100

150

200

Carboxytetrahydrocannabinol, di-butyl derivative C29H44O4 MW: 456.66

50

250 m/z

350

III-4-D-i

COOC 4H 9 OC 4H 9 H C 3 H C O 3

300

400

450

355.3

399.2

CH (CH ) CH 2 23 3

441.3 456.3

283.1

383.2


100

100

150

200

Carboxytetrahydrocannabinol-d3, di-butyl derivative C29H41D3O4 MW: 459.68

50

250

300

COOC 4H 9

III-4-D-ii

OC 4H 9 H C 3 H C O 3

350

400

450

500

358.3

CH (CH ) CD 2 23 3

402.3

444.3 459.3

286.2

386.2


100

100

150

200

Carboxytetrahydrocannabinol-d9, di-butyl derivative C29H35D9O4 MW: 465.71

50

250

300

400

450

500

364.3

COOC 4H 9

III-4-D-iii

OC 4H 9 D C 3 D C O 3

350

CH (CH ) CD 2 23 3

408.3

447.3 465.4

392.3

289.2

0 50

100

150

200

250

300 m/z



350

400

450

500

232


Relative Int. (%)

100

258.1 COOH

50

H C 3 H C O 3

Carboxytetrahydrocannabinol, propionyl derivative

314.1

III-4-E-i

OCOC 2H 5

C24H32O5 MW: 400.51

CH (CH ) CH 2 23 3

57.0

299.1

243.1

337.1

0 50

100

Relative Int. (%)

100

150

200

250

300

H C 3 H C O 3

400

450

Carboxytetrahydrocannabinol-d3, propionyl derivative

317.1

III-4-E-ii

OCOC 2H 5

50

350

258.1

COOH

370.2

C24H29D3O5 MW: 403.53

CH (CH ) CD 2 23 3

57.0

302.1

243.0

373.2

340.1

0 50

100

Relative Int. (%)

100

150

200

300

350

264.1

COOH

D C 3 D C O 3

C24H23D9O5 MW: 409.56 305.1

246.1

100

Relative Int. (%)

150

200

50

73.1

250 m/z

350

371.3

OSi(CH3)3 H C 3 H C O 3

C27H44O4Si2 MW: 488.81

300

COOSi(CH3)3

Carboxytetrahydrocannabinol, di-trimethylsilyl derivative

379.2

343.1

0

100

450

CH (CH ) CD 2 23 3

57.1

50

400

Carboxytetrahydrocannabinol-d9, propionyl derivative

323.2

III-4-E-iii

OCOC 2H 5

50

250

CH (CH ) CH 2 23 3

400

450

III-4-F-i 473.3 489.3

208.7

147.1

297.2 355.2

0 50

100

Relative Int. (%)

100

150

200

250

Carboxytetrahydrocannabinol-d3, di-trimethylsilyl derivative

50

73.1

C27H41D3O4Si2 MW: 491.83

300

400 374.3

COOSi(CH3)3 OSi(CH3)3 H C 3 H C O 3

CH (CH ) CD 2 23 3

450

500

550

III-4-F-ii 476.3 492.3

300.2

208.7

147.1

350

358.2

0 50

100

Relative Int. (%)

100

150

200

250

Carboxytetrahydrocannabinol-d9, di-trimethylsilyl derivative

50

73.1

300

450

500

550

III-4-F-iii

OSi(CH3)3 CH (CH ) CD 2 23 3

479.3 306.2

211.7

147.1

400 380.3

COOSi(CH3)3

D C 3 D C O 3

C27H35D9O4Si2 MW: 497.86

350

498.4

361.2

0 50

100

150

200

250

300 m/z

350



400

450

500

550

233


Relative Int. (%)

100

Carboxytetrahydrocannabinol, di-t-butyldimethylsilyl derivative

OSi(CH3)2C(CH3)3

C33H56O4Si2 MW: 572.97

73.1

50

H C 3 H C O 3

229.6

147.1

515.4

413.3

COOSi(CH3)2C(CH3)3

III-4-G-i

CH (CH ) CH 2 23 3

297.2

572.4

557.4

355.2 471.3

0 50

100

Relative Int. (%)

100

150

200

250

Carboxytetrahydrocannabinol-d3, di-t-butyldimethylsilyl derivative 73.1

50

300

350

500

550

600

518.4

OSi(CH3)2C(CH3)3

III-4-G-ii

CH (CH ) CD 2 23 3

229.7

147.1

450 416.4

COOSi(CH3)2C(CH3)3

H C 3 H C O 3

C33H53D3O4Si2 MW: 575.98

400

300.2

575.5

560.4

358.3 474.3

0 50

100

Relative Int. (%)

100

150

200

250

Carboxytetrahydrocannabinol-d9, di-t-butyldimethylsilyl derivative

350

450

500

550

600

524.4

422.4

OSi(CH3)2C(CH3)3

III-4-G-iii

CH (CH ) CD 2 23 3

581.5

364.3

232.7

147.1

400

COOSi(CH3)2C(CH3)3

D C 3 D C O 3

C33H47D9O4Si2 MW: 582.02

73.1

50

300

563.4

306.2

480.4

0 50

100

150

200

250

300

350

400

450

500

550

600


100

Carboxytetrahydrocannabinol, methyl/trifluoroacetyl derivative

III-4-H-i


C24H29F3O5 MW: 454.48

50

439.2

COOCH3

395.2

CH (CH ) CH 2 23 3

281.2

69.1

341.2 379.2

313.1

454.2

411.2

0 50

100

Relative Int. (%)

100

150

200

Carboxytetrahydrocannabinol-d3, methyl/trifluoroacetyl derivative

300

350

400

450

500

442.2

COOCH3

III-4-H-ii


C24H26D3F3O5 MW: 457.50

50

250

CH (CH ) CD 2 23 3

69.1

284.2

398.2

457.3

344.2 382.2

316.1

414.2

0 50

100

Relative Int. (%)

100

150

200

Carboxytetrahydrocannabinol-d9, methyl/trifluoroacetyl derivative C24H20D9F3O5 MW: 463.53

50

250

300

350

450

500

445.2

COOCH3

III-4-H-iii

OCOCF3 D C 3 D C O 3

400

404.3 CH (CH ) CD 2 23 3

69.1

290.2

463.3

350.3

316.1

385.2

414.2

0 50

100

150

200

250

300 m/z



350

400

450

500

234


Relative Int. (%)

100

459.2

COOCH2(C2F5) Carboxytetrahydrocannabinol, pentafluoro-1-propanyl/ OCOC 2F 5 445.2 pentafluoropropionyl derivative H C 3 CH (CH ) CH 429.1 H C O 2 23 3 119.1 C27H28F10O5 3 363.1 MW: 622.49 281.2

50 69.1

622.2

607.2

III-4-I-i 473.2 489.2

579.2

551.1

0 50

100

150

Relative Int. (%)

100

119.0

50 69.1

200

250

300

350

400

3 H C O 3

500

448.2

600 610.2

III-4-I-ii

650 625.3

476.2

CH (CH ) CD 432.2 2 23 3

492.2

366.1

284.2

550

462.2

Carboxytetrahydrocannabinol-d3, COOCH2(C2F5) pentafluoro-1-propanyl/ OCOC 2F 5 pentafluoropropionyl derivative H C C27H25D3F10O5 MW: 625.51

450

582.2

551.1

0 50

100

Relative Int. (%)

100

150

200

250

300

350

400

3 D C O 3

119.0 C27H19D9F10O5 MW: 631.55 75.2

454.3

CH (CH ) CD 2 23 3

366.1

289.2

500

550

600

468.3

Carboxytetrahydrocannabinol-d9, COOCH2(C2F5) pentafluoro-1-propanyl/ OCOC 2F 5 pentafluoropropionyl derivative D C

50

450

650

613.2

631.3

III-4-I-iii 482.3

498.3

432.2

582.2

557.2

0 50

100

Relative Int. (%)

100

150

200

250

Carboxytetrahydrocannabinol, hexafluoro-2-propanyl/ heptafluorobutyryl derivative

50

69.0 C28H27F13O5 MW: 690.49

300

400

450

500

477.2

COOCH(CF )2 3 OCOC 3F 7 H C 3 H C O 3

169.0

350 m/z

CH (CH ) CH 2 23 3

550

600

650

III-4-J-i 690.2

495.2 523.2 539.2

389.1

675.2

647.1

0 50

100

Relative Int. (%)

100

150

200

250

Carboxytetrahydrocannabinol-d3, hexafluoro-2-propanyl/ heptafluorobutyryl derivative

50

C28H24D3F13O5 MW: 693.51

69.0

300

400

450

500

550

600

650

700

750

480.2

COOCH(CF )2 3 OCOC 3F 7 H C 3 H C O 3

169.0

350

III-4-J-ii

CH (CH ) CD 2 23 3

693.2

498.2 526.2 542.2

678.2

392.1

650.1

0 50

100

Relative Int. (%)

100

150

200

250

Carboxytetrahydrocannabinol-d9, hexafluoro-2-propanyl/ heptafluorobutyryl derivative

50 75.1

300

400

450

500

550

486.2

COOCH(CF )2 3 OCOC 3F 7 D C 3 D C O 3

C28H18D9F13O5 MW: 699.54 169.0

350

CH (CH ) CD 2 23 3

600

650

700

750

III-4-J-iii

504.2 532.2 548.2

681.2

699.3

650.2

0 50

100

150

200

250

300

350

400 m/z

450



500

550

600

650

700

750

235

Figure III-5. Mass spectra of ketamine and its deuterated analogs (ketamine-d4): (A) underivatized; (B) acetylderivatized; (C) TFA-derivatized; (D) HFB-derivatized; (E) PFB-derivatized; (F) TMS-derivatized. Relative Int. (%)

100

180.0

Cl

Ketamine (CAS NO. 6740-88-1)

III-5-A-i

O

C13H16ClNO MW: 237.72

50

NH

182.0

CH 3

138.0

102.0

209.1

152.0

237.0


100

100

150

III-5-A-ii

D

Cl

C13H12D4ClNO MW: 241.75

250

184.1

D

Ketamine-d4

50

200

O D

D

186.1

NH

106.1

142.0

CH 3

213.1

156.0 241.1

0 50

100

Relative Int. (%)

100

Ketamine, acetyl derivative

150 m/z

C15H18ClNO2 MW: 279.76 115.0 56.2 75.1 102.1

50

180.1

152.1

III-5-B-i

200

208.1

250

Cl

216.2

O

N COCH 3

125.0

CH 3

251.1

279.2

0 50

100

Relative Int. (%)

100

150

Ketamine-d4, acetyl derivative

III-5-B-ii

C15H14D4ClNO2 MW: 283.78

50 56.1

200

250

300 D

220.2

184.1 212.1

Cl

D D N COCH 3

129.1

78.0 106.1 119.1

D

O

156.1

CH 3

255.1

283.3

0 50

100

150

200

250

300


100

110.1

Ketamine, trifluoroacetyl derivative

69.1

152.1

125.1

50 75.1

III-5-C-i

C15H15ClF3NO2 236.2 MW: 333.73 262.1 208.1 228.1 179.1

Cl

O

270.2 N COCF 3

298.2

305.1

CH 3

333.1

0 50

100

Relative Int. (%)

100

150

200

110.1 69.1

156.1 129.1

50 78.1

Ketamine-d4, trifluoroacetyl derivative

250

300 D

III-5-C-ii

C15H11D4ClF3NO2 240.2 MW: 337.75 266.2 212.2 232.2 183.1

Cl

100

150

200 m/z Figure III — Hallucinogens


250

D

O

274.2

302.2

0 50

350

300

309.2

D D N COCF 3 CH 3

337.2

350

236


Relative Int. (%)

100

210.0

Ketamine, heptafluorobutyryl derivative C17H13F7ClNO2 MW: 433.74

50 69.1

362.0

III-5-D-i

236.1 N COC 3 F 7

152.0

125.0

115.1

370.1

Cl

O

CH 3

398.1

328.1

434.1

0 50

100

Relative Int. (%)

100

150

200

Ketamine-d4, heptafluorobutyryl derivative

50

69.1

250

350

400

D

366.1

D

240.1

D N COC 3 F 7 CH 3

156.1

III-5-D-ii

374.2

O

129.1

450

D Cl

C17H9D4F7ClNO2 MW: 477.37 119.1

300

210.0

402.1

332.1

437.2

0 50

Relative Int. (%)

100

100

150

200

195.0

Ketamine, pentafluorobenzoyl derivative

50

350

400

368.1 360.0

Cl

450

III-5-E-i

208.0 N COC 6 F 5

167.0 178.0

125.0

102.1

300

O

152.0

C20H15ClF5NO2 MW: 431.79

250 m/z

CH 3

304.1

403.1 431.1

396.1

326.1


100

100

150

200

50

350

400

372.1 364.1

D Cl

D

208.0

D D N COC 6 F 5 CH 3

167.0 182.1

304.1

407.1 435.1

400.2

330.1

450

III-5-E-ii

O

156.1

129.1

106.1

300

195.0

Ketamine-d4, pentafluorobenzoyl derivative C20H11D4ClF5NO2 MW: 435.81

250

0 50

Relative Int. (%)

100

100

73.1

150

200

250 m/z

Ketamine, trimethylsilyl derivative

93.1

115.1

350

400

O

III-5-F-i

N Si(CH3)3 CH 3

278.2

153.1

182.1

198.3

243.2

266.2 309.1


100

100 73.1

150

200

Ketamine-d4, trimethylsilyl derivative

250

93.1

300

350 D Cl

III-5-F-ii

C16H20D4ClNOSi MW: 313.93

50

198.2 182.2

247.3

D

O

282.2

120.1 156.1

450

Cl

C16H24ClNOSi MW: 309.90

50

300

270.2

313.5

D D N Si(CH3)3 CH 3

0 50

100

150

200 m/z



250

300

350

237

Figure III-6. Mass spectra of norketamine and its deuterated analogs (norketamine-d4): (A) underivatized; (B) acetylderivatized; (C) TCA-derivatized; (D) TFA-derivatized; (E) PFP-derivatized; (F) HFB-derivatized; (G) 4-CB-derivatized; (H) PFB-derivatized; (I) TMS-derivatized; (J) TFA/t-BDMS-derivatized; (K) PFP/t-BDMS-derivatized ; (L) HFB/tBDMS-derivatized. Relative Int. (%)

100

166.0

Norketamine

III-6-A-i

Cl

C12H14ClNO MW: 223.70

O

50

NH2

168.0

195.1

131.0

102.0

223.0


100

100

150

Norketamine-d4

200

D

C12H10D4ClNO MW: 227.72

250

170.0

Cl

III-6-A-ii

D

O

50

D

D NH2

172.0

199.1

135.1

106.1

227.1

0 50

Relative Int. (%)

100

100

150 m/z

Norketamine, acetyl derivative

250

202.2

166.1

III-6-B-i

230.2 Cl

C14H16ClNO2 MW: 265.73

50

200

75.1

O

138.1

102.1

160.1 NH

194.1

115.1

COCH 3


100

100

150

Norketamine-d4, acetyl derivative

250

300

206.2

III-6-B-ii

234.2

170.2

D

Cl

D

O

C14H12D4ClNO2 MW: 269.75

50

200

106.1

78.1

142.1

164.2

D

198.2

119.2

D

NH COCH 3

0 50

100

150

200

250

300


100

Norketamine, trichloroacetyl derivative C14H13Cl4NO2 MW: 369.07 102.0

50

304.0

Cl

334.0

O D

125.0

III-6-C-i

NH

179.0

COCCl 3

239.9


100

100

150

200

Norketamine-d4, trichloroacetyl derivative C14H9D4Cl4NO2 MW: 373.09

50

250 Cl

D

300

350

400

308.0 D

338.0

O D

129.0

106.0

D

III-6-C-ii

NH

183.0

COCCl 3

244.0

0 50


100

150

200


300

350

400

238

Figure III-6. (Continued) Relative Int. (%)

100

69.1

Cl

102.1

O

115.1

50

75.1

III-6-D-i

214.1 D

138.1

239.2

NH

125.1

COCF 3

167.1

194.1

Norketamine, trifluoroacetyl derivative

284.2

256.2

222.2

275.2

C14H13F3ClNO2 MW: 319.70

262.2

319.1

0 50

100

Relative Int. (%)

100

150

200

69.1 106.1

D

Cl

250

III-6-D-ii

D

O

218.2

119.2 129.1 142.1

50 78.2

D

D

300

350 Norketamine-d4, trifluoroacetyl derivative

288.2

260.2 243.2

279.2

C14H9D4F3ClNO2 MW: 323.73

NH

171.2

198.1

COCF 3

266.2

226.1

323.1

0 50

Relative Int. (%)

100

100

150

Norketamine, pentafluoropropionyl derivative

200 m/z

350

334.1 306.1

O

264.0

D

III-6-E-i

325.0

290.0

NH

149.0

115.1

102.0

300

Cl

C15H13ClF5NO2 MW: 369.71

50

250

COC 2 F 5

222.1

369.0


100

100

150

200

Norketamine-d4, pentafluoropropionyl derivative

Cl

300

350

D

119.0

310.1

D

268.0

D

III-6-E-ii

329.0

294.1

NH

147.1

106.1

400

338.1

O

C15H9D4ClF5NO2 MW: 373.74

50

D

250

226.1

COC 2 F 5

373.1

0 50

100

150

200

250

300

350

400


100

Norketamine, heptafluorobutyryl derivative

50

69.1

O

314.1

C16H13F7ClNO2 MW: 419.72 102.1

115.1

194.1

340.1 375.1

NH

149.0

384.1

356.1

Cl

III-6-F-i

COC 3 F 7

222.1

419.0

0 50

100

Relative Int. (%)

100

150

200

250 Cl

360.1

106.1

119.1

318.1

C16H9D4F7ClNO2 MW: 423.74

400

D

344.1 379.1

D

III-6-F-ii

NH

153.1 198.1

226.1

COC 3 F 7

423.1

0 50

100

150

200

250 m/z

300



450

388.1

D

O

69.1

350

D

Norketamine-d4, heptafluorobutyryl derivative

50

300

350

400

450

239


Relative Int. (%)

100

Norketamine, 4-carboethoxyhexafluorobutyryl derivative

O

438.1

C19H18ClF6NO4 MW: 473.79

50

410.1

Cl

NH

125.0

CO(CF2)3COOC2H 5

222.1

179.1

102.1

III-6-G-i

429.1

368.1 393.1


100

100

150

200

250

Norketamine-d4, 4-carboethoxyhexafluorobutyryl derivative C19H14D4ClF6NO4 MW: 477.82

50

300

350

400

450

D D

Cl

O

442.1 D

D

226.1

183.1

106.1

372.1 397.1

CO(CF2)3COOC2H 5

III-6-G-ii

433.1

NH

129.1

477.1

0 50

100

150

200

500

414.2

250

300

350

400

450

500

m/z

Relative Int. (%)

100

195.0

Norketamine, pentafluorobenzoyl derivative

167.0

102.1

75.1

382.1

O

C19H13ClF5NO2 MW: 417.76

50

354.1 Cl

III-6-H-i

NH

138.0

346.0

312.1

COC 6 F 5

417.0


100

100

150

200

D

167.0

106.1

142.1

78.1

Relative Int. (%)

100

200

386.1

350.1

316.1

421.1

300

350

Relative Int. (%)

100 73.1

138.1

III-6-I-i 210.1

225.1 267.2

Si(CH3)3

150 Norketamine-d4, trimethylsilyl derivative

93.0

Cl

D

200

250

D

242.2

100

D

142.1

150

214.2

350

229.2 271.2

Si(CH3)3

200 m/z



300

III-6-I-ii 284.2

0 50

295.2

D

NH

106.2 119.1

280.2

O

C15H18D4ClNOSi MW: 299.90

50

450

238.2

0 50

400

Cl

NH

115.2

III-6-H-ii

O

C15H22ClNOSi MW: 295.87 93.1 102.1

D

250 m/z

Norketamine, trimethylsilyl derivative

50

450

358.1 D

COC 6 F 5

150

73.1

100

400

NH

0

100

D

Cl

350

O

C19H9D4ClF5NO2 MW: 421.78

50

300

195.0

Norketamine-d4, pentafluorobenzoyl derivative

50

250

250

299.3

300

350

240


100

Norketamine, trifluoroacetyl/ t-butyldimethylsilyl derivative 73.1

C20H27ClF3NO2Si MW: 433.97

50

125.0

236.0

O

263.0

224.0

169.0

Cl

376.0

III-6-J-i

NCOCF3

274.0

336.1

308.0

Si(CH3)2C(CH3)3

433.1

0 50

100

Relative Int. (%)

100

150

200

250

300

Norketamine-d4, trifluoroacetyl/ t-butyldimethylsilyl derivative

73.0

400 380.1

236.0

C20H23D4ClF3NO2Si MW: 437.99 129.0

50

350

III-6-J-ii

Cl

267.0 278.0

D D NCOCF3

340.1

312.0

Si(CH3)2C(CH3)3

437.2

0 50


D

O

224.0

173.1

450 D

100

150

200

250 m/z

73.1 Norketamine, pentafluoropropionyl/ t-butyldimethylsilyl derivative C21H27ClF5NO2Si MW: 483.97 125.0

50

300

350

400 426.1

Cl O

286.0 296.0

263.0 220.0

450

III-6-K-i

324.0

169.0

NCOC 2F 5

358.0 Si(CH ) C(CH ) 32 33

190.0

483.2

0 50

100

Relative Int. (%)

100

150

200

250

300

Norketamine-d4, pentafluoropropionyl/ t-butyldimethylsilyl derivative

73.1

C21H23D4ClF5NO2Si MW: 488.00 129.0

50

350

400 Cl

267.1

286.0 300.0

220.1

D

450

500

430.1 D

O

173.1

III-6-K-ii

D D NCOC 2F 5

328.0 362.0

Si(CH3)2C(CH3)3

487.2

0 50

100

150

200

250

300

350

400

450

500


100 73.1

C22H27ClF7NO2Si MW: 533.98 125.0

50

476.1

Cl

Norketamine, heptafluorobutyryl/ tbutyldimethylsilyl derivative

O

336.0

263.0

374.0

190.0

NCOC 3F 7

408.0

III-6-L-i

Si(CH3)2C(CH3)3

533.2


100

100

150

200

250

300

Norketamine-d4, heptafluorobutyryl/ t-butyldimethylsilyl derivative

73.1

C22H23D4ClF7NO2Si MW: 538.01 194.0 129.0

50

350

400 Cl

336.0

267.0

450 D

550

480.1 D

O

D D NCOC 3F 7

378.1

500

III-6-L-ii

412.0 Si(CH ) C(CH ) 32 33

537.2

0 50

100

150

200

250

300 m/z

350



400

450

500

550

241

Figure III-7. Mass spectra of phencyclidine and its deuterated analogs (phencyclidine-d5): (A) underivatized. Relative Int. (%)

100

200.1

III-7-A-i

C17H25N MW: 243.38

50

243.2

91.1 84.1

Phencyclidine (CAS NO. 77-10-1)

N

166.1

117.1

186.1

0 50

100

150

200

Relative Int. (%)

100

205.2

D

D

96.1 84.1

C17H20D5N MW: 248.41

N

50

D

166.1

122.1

300 Phencyclidine-d5

D

D

III-7-A-ii

250

190.1

248.2

0 50

100

150

200 m/z



250

300

242

Figure III-8. Mass spectra of LSD and its deuterated analogs (LSD-d3): (A) underivatized-derivatized; (B) TMSderivatized. Relative Int. (%)

100

221.1

O H 5C 2 N C H 5C 2

44.1

H

50

181.1

72.1

N H


LSD (CAS NO. 50-37-3) C20H25N3O MW: 323.43

207.0

140

190

240

290

O H 5C 2 N C H 5C 2 H

N

LSD-d3 C20H22D3N3O MW: 326.45

181.0 207.0

44.0

N

72.0

128.1

H

40

90

100 73.1

167.0

140 O 5H 2C N C 5H 2C H

190 m/z

240

CH 3 H

N

0 50

100

207.0

Si(CH3)3

150

200

337.2

250

O 5H 2C N C 5H 2C H

73.1

CD 3 H

N

LSD-d3, trimethylsilyl derivative

271.1 279.1

C23H30D3N3OSi MW: 398.63

207.0

Si(CH3)3

350

296.1

III-8-B-ii

50 128.1

300 253.1

N

395.2

C23H33N3OSi MW: 395.61

279.1 268.1

128.1

340

LSD, trimethylsilyl derivative

293.1

III-8-B-i

50

100

290

253.1 N

340 326.2

224.1

III-8-A-ii

CD 3 H

50

0

Relative Int. (%)

323.2

167.1

128.1

90

100

Relative Int. (%)

III-8-A-i

CH 3 N H

400 398.2

337.2

0 50

100

150

200

250 m/z



300

350

400

243

Figure III-9. Mass spectra of mescaline and its deuterated analogs (mescaline-d9): (A) acetyl-derivatized; (B) TCAderivatized; (C) TFA-derivatized; (D) PFP-derivatized; (E) HFB-derivatized; (F) 4-CB-derivatized; (G) [TMS]2derivatized; (H) t-BDMS-derivatized; (I) TFA/TMS-derivatized; (J) TFA/t-BDMS-derivatized; (K) PFP/TMS-derivatized; (L) PFP/t-BDMS-derivatized; (M) HFB/TMS-derivatized; (N) HFB/t-BDMS-derivatized. Relative Int. (%)

100

Mescaline (CAS NO. 54-04-6), acetyl derivative

194.1 CH 2–CH 2–NHCOCH 3

CH3O

C13H19NO4 MW: 253.30

III-9-A-i

181.1

179.0

50

OCH OCH3 3

253.1

151.0

148.0

0 50

100

150

200

Relative Int. (%)

100

250

300

203.1

Mescaline-d9, acetyl derivative

CH 2–CH 2–NHCOCH 3

50

CD3O

185.1

OCD OCD3 3

190.1

C13H10D9NO4 MW: 262.23

III-9-A-ii

262.2

157.1

152.1

0 50

100

150

200

250

300


100

181.0

Mescaline, trichloroacetyl derivative

194.0

CH 2–CH 2–NHCOCCl 3

III-9-B-i 50

CH3O

C13H16Cl3NO4 MW: 356.62

OCH OCH3 3

151.0

148.0

357.0

354.9

238.0

0 50

100

150

200

Relative Int. (%)

100

190.1

250

300

350

CH 2–CH 2–NHCOCCl 3

C13H7D9Cl3NO4 MW: 365.55

III-9-B-ii

50

CD3O

400

Mescaline-d9, trichloroacetyl derivative

203.1

OCD OCD3 3

364.0

366.0

247.1

157.1

152.0

0 50

100

150

200

250

300

350

400


100

181.1

Mescaline, trifluoroacetyl derivative

CH 2–CH 2–NHCOCF 3

III-9-C-i 50

CH3O

OCH OCH3 3

194.1

307.1

C13H16F3NO4 MW: 307.27

179.1 151.1

148.0

0 50

100

150

200

Relative Int. (%)

100

250

190.1

300

Mescaline-d9, trifluoroacetyl derivative

CH 2–CH 2–NHCOCF 3

III-9-C-ii 50

CD3O

OCD OCD3 3

316.1

203.1 152.1

350

C13H7D9F3NO4 MW: 316.20

185.1 157.1

0 50

100

150



250

300

350

244

Figure III-9. (Continued) Ralative Int. (%)

100

181.1

Mescaline, pentafluoropropionyl derivative

50

C14H16F5NO4 MW: 357.27

194.1

CH3O

179.1

119.0

CH 2 –CH 2 –NHCOC 2 F 5

III-9-D-i

OCH OCH3 3

357.1

151.1

148.0


100

100

150

200

203.1

CD3O

185.1

400

100

III-9-D-ii 366.1

OCD OCD3 3

157.1

152.1

119.0

50

350


C14H7D9F5NO4 MW: 366.20

0

300

190.1

Mescaline-d9, pentafluoropropionyl derivative

50

250

150

200

250

300

350

400


100

181.1

Mescaline, heptafluorobutyryl derivative

50

194.1

C15H16F7NO4 MW: 407.28

III-9-E-i


CH3O

179.1

OCH OCH3 3

407.1

151.1


100

100

150

200

Mescaline-d9, heptafluorobutyryl derivative

50

250

300

350

400

450

190.2 CH 2 –CH 2 –NHCOC 3 F 7

203.1

C15H7D9F7NO4 MW: 416.21

CD3O

185.1

III-9-E-ii

OCD OCD3 3

416.2

157.1

0 50

Relative Int. (%)

100

100

150

181.1

Mescaline, 4-carboethoxyhexafluorobutyryl derivative

50

C18H21F6NO6 MW: 461.35

200

250 m/z

300

194.1

350

Relative Int. (%)

100

100

III-9-F-i CH3O

OCH OCH3 3

151.1

150

200

250

300

203.2

350

OCD OCD3 3

157.1

500

150

470.2 425.1

200

250

300 m/z



450

III-9-F-ii CD3O

0 100

400

CH 2–CH2–NHCO(CF2)3COOC 2H 5

185.1

C18H12D9F6NO6 MW: 470.28

50

461.1 416.1

190.2

Mescaline-d9, 4-carboethoxyhexafluorobutyryl derivative

50

450

CH 2–CH2–NHCO(CF2)3COOC 2H 5

0 50

400

350

400

450

500

245


100

Mescaline, di-trimethylsilyl derivative

174.1 CH 2–CH 2–N–Si(CH3)3

III-9-G-i

Si(CH3)3

50

CH3O

73.1

C17H33NO3Si2 MW: 355.62

OCH OCH3 3

340.2

86.1

354.2

0 50

100

150

200

Relative Int. (%)

100

250

300

350

174.1 Si(CH3)3

50

CD3O

73.1

Mescaline-d9, di-trimethylsilyl derivative

CH 2–CH 2–N–Si(CH3)3

III-9-G-ii

C17H24D9NO3Si2 MW: 364.46 349.2 363.2

OCD OCD3 3

86.1

0 50

100

150

200

400

250

300

350

400


100

144.1

50

Mescaline, t-butyldimethylsilyl derivative

CH2–CH2–NHSi(CH3)2C(CH3)3

III-9-H-i CH3O

73.1 88.1

OCH OCH3 3

181.1

209.1

310.2

0 50

100

150

Relative Int. (%)

100

200

250

CD3O

73.1 88.1

212.1

181.1

319.2

0 50

Relative Int. (%)

100

100

150

Mescaline, trifluoroacetyl/trimethylsilyl derivative

200 m/z

250

334.2

300

350

181.1 CH 2 –CH 2 –N–COCF 3

III-9-I-i

Si(CH3)3

C16H24F3NO4Si MW: 379.45 73.0

50

C17H22D9NO3Si MW: 334.45

277.2

OCD OCD3 3

350

Mescaline-d9, t-butyldimethylsilyl derivative

CH 2–CH2–NHSi(CH3)2C(CH3)3

50

325.0

300

144.1

III-9-H-ii

C17H31NO3Si MW: 325.52

268.1

CH3O

OCH OCH3 3

379.1

198.0


100

100

150

Mescaline-d9, trifluoroacetyl/trimethylsilyl derivative

50

200

250

300

350

400

190.1 CH 2 –CH 2 –N–COCF 3

III-9-I-ii

Si(CH3)3

C16H15D9F3NO4Si MW: 388.38 73.0

CD3O

OCD OCD3 3

388.2

203.1

0 50

100

150

200

250 m/z



300

350

400

246


Relative Int. (%)

100

Mescaline, trifluoroacetyl/ t-butyldimethylsilyl derivative

50

C19H30F3NO4Si MW: 421.53 73.0

181.1

III-9-J-i

CH 2 –CH 2 –N–COCF 3 Si(CH3)2C(CH3)3 CH3O

OCH OCH3 3

195.1 220.1 240.1

148.0

421.2

268.0


100

100

150

200

C19H21D9F3NO4Si MW: 430.46 73.0

300

350

400

190.1

Mescaline-d9, trifluoroacetyl/ t-butyldimethylsilyl derivative

50

250

450

III-9-J-ii

CH 2 –CH 2 –N–COCF 3

Si(CH3)2C(CH3)3 CD3O

204.1 229.1

152.0

249.1

OCD OCD3 3

430.2

277.1

0 50

100

Relative Int. (%)

100

Mescaline, pentafluoropropionyl/ trimethylsilyl derivative

50

50

100


200

50

100

100

CH3O

195.1

150

50

C20H30F5NO4Si MW: 471.53

400

450

III-9-K-i

OCH OCH3 3

429.1

248.0

200

250

300

350

400

190.1

450

III-9-K-ii



204.1

150

Mescaline, pentafluoropropionyl/ t-butyldimethylsilyl derivative

350

Si(CH3)2C(CH3)3

C17H15D9F5NO4Si MW: 438.38 73.0 152.0

0

300


Mescaline-d9, pentafluoropropionyl/ trimethylsilyl derivative

50

250 m/z

181.1

C17H24F5NO4Si MW: 429.45 73.0 148.0

0

Relative Int. (%)

150

200

OCD OCD3 3

248.0

250 m/z

181.1

438.2

300

350

400

CH 2 –CH 2 –N–COC 2 F 5

III-9-L-i

Si(CH3)2C(CH3)3

195.1

CH3O

OCH OCH3 3

73.0

290.1

450

471.2

318.0

414.1


100

100

150

Mescaline-d9, pentafluoropropionyl/ t-butyldimethylsilyl derivative

50

200

250

190.1

300

350

400

CH 2 –CH 2 –N–COC 2 F 5

204.1

CD3O

III-9-L-ii

OCD OCD3 3

73.0

299.1

480.2

327.1

423.1

0 100

150

200

250

300 m/z



500

Si(CH3)2C(CH3)3

C20H21D9F5NO4Si MW: 480.46

50

450

350

400

450

500

247


100

Mescaline, heptafluorobutyryl/ trimethylsilyl derivative

50 73.0

181.0

CH 2 –CH 2 –N–COC 3 F 7

III-9-M-i

Si(CH3)3 CH3O

C18H24F7NO4Si MW: 479.46 195.0

OCH OCH3 3

479.1

298.0

0 50

100

Relative Int. (%)

100

150

200

73.0

300

350

190.1

Mescaline-d9, heptafluorobutyryl/ trimethylsilyl derivative

50

250

400

450

500

CH 2 –CH 2 –N–COC 3 F 7

III-9-M-ii

Si(CH3)3 CD3O

C18H15D9F7NO4Si MW: 488.39 204.1

OCD OCD3 3

488.2

298.0

0 50

100

150

200

250

300

350

400

450

500

m/z Ralative Int. (%)

100

181.0

III-9-N-i

Si(CH3)2C(CH3)3

50

CH3O

195.0

73.0

0 50

100

150

Ralative Int. (%)

200

250

300

190.1

III-9-N-ii

350

204.1

73.0

349.1

0 100

150

200

250

300 m/z

350



450

550

C21H21D9F7NO4Si MW: 530.47 530.2

377.1

400

500

Mescaline-d9, heptafluorobutyryl/ t-butyldimethylsilyl derivative

OCD OCD3 3

326.1

50

400


521.2

340.0 368.0

CH 2 –CH 2 –N–COC 3 F 7

50

C21H30F7NO4Si MW: 521.54

OCH OCH3 3

317.0

100

Mescaline, heptafluorobutyryl/ t-butyldimethylsilyl derivative

CH 2 –CH 2 –N–COC 3 F 7

450

500

550

248

Figure III-10. Mass spectra of psilocin and its deuterated analogs (psilocin-d10): (A) underivatized; (B) acetylderivatized; (C) [acetyl]2-derivatized; (D) [TMS]2-derivatized; (E) t-BDMS-derivatized; (F) [t-BDMS]2-derivatized. Relative Int. (%)

100

58.1

Psilocin (CAS NO. 520-53-6)

OH

CH 3

CH 2CH 2N

III-10-A-i

50

C12H16N2O MW: 204.26

CH 3

N H

204.1

146.0

0 50

100

Relative Int. (%)

100

150

66.1

200

OH

III-10-A-ii

Psilocin-d10

CD 3

CD 2CD 2N

50

250

C12H6D10N2O MW: 214.32

CD 3

N H

214.2

148.1

0 50

Relative Int. (%)

100

100

150 m/z

58.1

200

Psilocin, acetyl derivative

COCH 3 O

III-10-B-i

50

CH 3

CH 2CH 2N

C14H18N2O2 MW: 246.30

CH 3

N H

146.1

246.1


250

100

150

66.1

200

250

COCH 3 O

III-10-B-ii

50

300 Psilocin-d10, acetyl derivative

CD 3

CD 2CD 2N

C14H8D10N2O2 MW: 256.36

CD 3

N H

148.1

0 50

100

150

256.2

200

250

300


100

58.1

COCH 3

O

III-10-C-i

Psilocin, di-acetyl derivative

CH 3

CH 2CH 2N

C16H20N2O3 MW: 288.34

CH 3

50 N

Si(CH3)2C(CH3)3

146.0

0 50 100

100

160.1

288.1

150

66.1

200

250

COCH 3 O

III-10-C-ii

CD 2CD 2N

50

300 Psilocin-d10, di-acetyl derivative

CD 3 CD 3

C16H10D10N2O3 MW: 298.40

N Si(CH3)2C(CH3)3

148.1

0 50

100

165.1

150

298.2

200 m/z



250

300

249


100

290.2

Si(CH3)3 O

58.1

CH 3

CH 2CH 2N

50 73.1

C18H32N2OSi2 MW: 348.63

CH 3

N

348.2

Si(CH3)3

0 50

100

202.1

174.0

150

333.2

200

250

300


Psilocin, di-trimethylsilyl derivative

III-10-D-i

Si(CH3)3

66.2

O

73.1

C18H22D10N2OSi2 MW: 358.69 358.3

CD 3

N Si(CH3)3

0 50

100

150

343.2

204.1

175.1

400

Psilocin-d10, di-trimethylsilyl derivative

III-10-D-ii

CD 3

CD 2CD 2N

50

350

292.2

200

250

300

350

400


100

58.1

Psilocin, t-butyldimethylsilyl derivative

Si(CH3)2C(CH3)3 O

III-10-E-i

CH 3

CH 2CH 2N

50

C18H30N2OSi MW: 318.52

CH 3

N

188.1

H

73.1

202.1

0 50

100

Relative Int. (%)

100

66.2

250

300

CD 2CD 2N

50

CD 3

III-10-E-ii

CD 3

C18H20D10N2OSi MW: 328.59 328.2

N H

73.1

100

100

58.1

150

261.1

200 m/z

250

300

CH 2CH 2N

73.1

III-10-F-i

CH 3

375.2

CH 3

350

Psilocin, di-t-butyldimethylsilyl derivative

Si(CH3)2C(CH3)3 O

50

204.1

190.1

350 Psilocin-d10, t-butyldimethylsilyl derivative

Si(CH3)2C(CH3)3

50

N

C24H44N2OSi2 MW: 432.79

Si(CH3)2C(CH3)3

432.3

177.1


200

O

0

Relative Int. (%)

150

318.2

259.1

100

150

200

300

350

Si(CH3)2C(CH3)3

66.1

O CD 2CD 2N

73.1

50

250

CD 3

III-10-F-ii 376.2

CD 3

400

Psilocin-d10, di-t-butyldimethylsilyl derivative C24H34D10N2OSi2 MW: 442.85

N

Si(CH3)2C(CH3)3

442.3

179.1

0 50

100

150

200

250 m/z



450

300

350

400

450

251

Summary of Drugs, Isotopic Analogs, and Chemical Derivatization Groups Included in Figure IV (Depressants/Hypnotics) Compound

Isotopic analog

Pentobarbital

d5

Phenobarbital

d5, d5 (ring)


Figure #

None, [methyl]2, [ethyl]2, [propyl]2, [butyl]2, [TMS]2, [t-BDMS]2 (14)

IV-1

[Methyl]2, [ethyl]2, [propyl]2, [butyl]2, [TMS]2, [t-BDMS]2 (18)

IV-2

d 5,

13C

4


IV-3

Sceobarbital

d 5,

13C

4


IV-4

Methohexital

d5

None, methyl, ethyl, propyl, butyl, TMS, t-BDMS (14)

IV-5

γ-Hydroxybutyric acid d6

[TMS]2, [t-BDMS]2 (4)

IV-6

γ-Butyrolactone

None (2)

IV-7

Butabital

d6


Figure IV — Depressants/Hypnotics


253

Appendix One — Figure IV Mass Spectra of Commonly Abused Drugs and Their Isotopically Labeled Analogs in Various Derivatization Forms — Depressants/Hypnotics Figure IV-1. Mass spectra of pentobarbital and its deuterated analogs (pentobarbital-d5): (A) underivatized; (B) [methyl]2derivatized; (C) [ethyl]2-derivatized; (D) [propyl]2-derivatized; (E) [butyl]2-derivatized; (F) [TMS]2-derivatized; (G) [t-BDMS]2-derivatized .......................................................................................................................................................... 254 Figure IV-2. Mass spectra of phenobarbital and its deuterated analogs (phenobarbital-d5, -d5 ring): (A) [methyl]2derivatized; (B) [ethyl]2-derivatized; (C) [propyl]2-derivatized; (D) [butyl]2-derivatized; (E) [TMS]2-derivatized; (F) [t-BDMS]2-derivatized ............................................................................................................................................................ 257 Figure IV-3. Mass spectra of butabital and its deuterated analogs (butabital-d5, -13C4): (A) underivatized; (B) [methyl]2derivatized; (C) [ethyl]2-derivatized; (D) [propyl]2-derivatized; (E) [butyl]2-derivatized; (F) [TMS]2-derivatized; (G) [t-BDMS]2-derivatized ........................................................................................................................................................... 260 Figure IV-4. Mass spectra of secobarbital and its deuterated analogs (secobarbital-d5, -13C4): (A) underivatized; (B) [methyl]2-derivatized; (C) [ethyl]2-derivatized; (D) [propyl]2-derivatized; (E) [butyl]2-derivatized; (F) [TMS]2-derivatized; (G) [t-BDMS]2-derivatized ........................................................................................................................................................... 264 Figure IV-5. Mass spectra of methohexital and its deuterated analogs (methohexital-d5): (A) underivatized; (B) methylderivatized; (C) ethyl-derivatized; (D) propyl-derivatized; (E) butyl-derivatized; (F) TMS-derivatized; (G) t-BDMSderivatized ..................................................................................................................................................................................... 268 Figure IV-6. Mass spectra of γ-hydroxybutyric acid (GHB) and its deuterated analogs (GHB-d6): (A) [TMS]2-derivatized; (B) [t-BDMS]2-derivatized ........................................................................................................................................................... 271 Figure IV-7. Mass spectra of γ-butyrolactone (GBL) and its deuterated analogs (GBL-d6) ...................................................... 272



254

Figure IV-1. Mass spectra of pentobarbital and its deuterated analogs (pentobarbital-d5): (A) underivatized; (B) [methyl]2-derivatized; (C) [ethyl]2-derivatized; (D) [propyl]2-derivatized; (E) [butyl]2-derivatized; (F) [TMS]2derivatized; (G) [t-BDMS]2-derivatized. Relative Int. (%)

100

H

IV-1-A-i H 3C

50

O

H 3C H 2C H 2C H 2C HC

156.0

141.0

Pentobarbital (CAS NO.76-74-4)

O

N

C11H18N2O3 MW: 226.13

N H

O

CH 3

55.0

98.0

69.0

197.0


100

100

H 3C

H 2C

O

D 3C D 2C H 2C HC

161.0

Pentobarbital-d5 (CAS NO.52944-66-8) C11H13D5N2O3 MW: 231.30

143.0 H

O

100.0

71.1

250

O

N

N

CH 3

55.1

200

H

IV-1-A-ii

50

150

197.1

0 50

100

150 m/z

Relative Int. (%)

100

IV-1-B-i 50

H 3C

H 3C H 2C H 2C HC

H 2C

97.0

Pentobarbital, di-methyl derivative

184.0

C13H22N2O3 MW: 254.33

N CH 3

O

CH 3

69.0

250

169.0

CH 3 O N

O

200

112.0

225.1

0 50

100

150

Relative Int. (%)

100

IV-1-B-ii 50

H 3C

CH 3 O N

O D 3C D 2C H 2C HC

H 2C

74.1

0 50

171.0

250

189.1

300 Pentobarbital-d5, di-methyl derivative C13H17D5N2O3 MW: 259.36

N

CH 3

102.0

200

CH 3

O

114.0

225.1

100

150

200

250

300


100

IV-1-C-i 50

H 3C

O

H 2C

H 3C H 2C H 2C HC

Pentobarbital, di-ethyl derivative

212.2

C15H26N2O3 MW: 282.37

N

CH 3

97.1

69.1

197.1

C 2H 5 O N C 2H 5

O

253.2

169.1

126.1


100

100

150

IV-1-C-ii

50

H 3C

O H 2C

D 3C D 2C H 2C HC

102.1

70.1

50

100

217.2

C 2H 5 O N

300 Pentobarbital-d5, di-ethyl derivative

199.1

C15H21D5N2O3 MW: 287.40

O

C 2H 5

253.2

171.1

128.1

150

200 m/z



250

N

CH 3

0

200

250

300

255

Figure IV-1. (Continued)

Relative Int. (%)

100

IV-1-D-i H 3C

50

H 2C

C 3H 7 O N

O H 3C H 2C H 2C HC

N

CH 3

97.1 69.1

Pentobarbital, di-propyl derivative C17H30N2O3 MW: 310.43

156.1

C 3H 7

O

240.2

198.1

225.2

181.1

141.1

281.2

309.2


100

100

150

IV-1-D-ii

50

C 3H 7 O N

O D 3C D 2C H 2C HC

H 2C

H 3C

300

245.2

350

Pentobarbital-d5, di-propyl derivative C17H25D5N2O3 MW: 315.46

161.1

C 3H 7

O

250 203.2

N

CH 3

102.1 74.1

200

227.2

185.1

143.1

281.2

315.2

0 50

Relative Int. (%)

100

100

150

IV-1-E-i H 3C

50

H 3C H 2C H 2C HC

97.1 69.1

250

300

251.2

C 4H 9 O N

O

H 2C

200 m/z

Pentobarbital, di-butyl derivative

268.2

195.1

350

N

CH 3

C19H34N2O3 MW: 338.48

C 4H 9

O

156.1

213.2

309.3

170.1

141.1

337.3


100

100

150

IV-1-E-ii H 3C

50

O

H 2C

D 3C D 2C H 2C HC

102.1 74.1

50

Relative Int. (%)

100

256.3

CH 3

O

100.0

Pentobarbital-d5, di-butyl derivative 273.3

C19H29D5N2O3 MW: 343.51

218.2

161.1

309.3

175.1

150

200 m/z

H 3C

H 2C

250

H 3C H 2C H 2C HC

300

Si(CH3)3

300.1

269.1

147.0

350

IV-1-F-i

N O

343.3

285.1

Si(CH3)3 O N

O

CH 3

73.0

350

C 4H 9

Pentobarbital, di-trimethylsilyl derivative

50

300

N

100

C17H34N2O3Si2 MW: 370.63

250

200.2

143.1

0

200

C 4H 9 O N

355.2 341.2

370.2


100

100

150

200

Pentobarbital-d5, di-trimethylsilyl derivative C17H29D5N2O3Si2 MW: 375.66

50

73.1

250

H 3C

H 2C

D 3C D 2C H 2C HC

100.0

O

147.0

400

IV-1-F-ii

305.2

N

CH 3

350

290.1

Si(CH3)3 O N

O

300

360.2

Si(CH3)3

274.1

341.2

375.3

0 50

100

150

200

250 m/z



300

350

400

256


Relative Int. (%)

100

Pentobarbital, di-t-butyldimethylsilyl derivative C23H46N2O3Si2 MW: 454.79

50

Si(CH3)2C(CH3)3 O N

O

H 3C

H 2C

H 3C H 2C H 2C HC

100.1

IV-1-G-i

N

Si(CH3)2C(CH3)3

O

CH 3

73.1

397.3 327.2

269.1

439.3

369.2

174.1

454.4


100

100

150

200

Pentobarbital-d5, di-t-butyldimethylsilyl derivative C23H41D5N2O3Si2 MW: 459.82

50

73.1

H 3C

250

Si(CH3)2C(CH3)3 O N

O D 3C D 2C H 2C HC

H 2C

350

400

450

332.2

IV-1-G-ii

O

Si(CH3)2C(CH3)3

274.1

174.1

444.3

374.3

459.4

0 50

100

150

200

250

300 m/z



500

402.3

N

CH 3

100.1

300

350

400

450

500

257

Figure IV-2. Mass spectra of phenobarbital and its deuterated analogs (phenobarbital-d5, -d5 ring): (A) [methyl]2derivatized; (B) [ethyl]2-derivatized; (C) [propyl]2-derivatized; (D) [butyl]2-derivatized; (E) [TMS]2-derivatized; (F) [t-BDMS]2-derivatized.

Relative Int. (%)

100 H 3C

50

CH 3 O N

O H 2C

Phenobarbital (CAS NO.50-06-6), di-methyl derivative

N

103.0

77.0

IV-2-A-i

C14H16N2O3 MW: 260.28

CH 3

O

232.1

117.0

146.0

175.0

188.0

245.0

0 50

100

Relative Int. (%)

100

50

200

CH 3

105.0

122.1

151.1

176.0

233.1

IV-2-A-ii

190.0

77.0

247.1

0 50

100

Relative Int. (%)

100 H 3C

50

D

D

200

CH 3

108.1

180.0

151.1

123.1

82.0

0 50

300

237.1

VI-2-A-iii

C14H11D5N2O3 MW: 265.31

N

D

265.1

250

Phenobarbital-d5, di-methyl derivative

N

DO

D

150

CH 3 O

O H 2C

300

C14H11D5N2O3 MW: 265.31

N

O

250

Phenobarbital-d5 (CAS NO.52944-66-8), di-methyl derivative

CH 3 O N

O D 2C

D 3C

150

260.1

100

150

193.1

250.1 265.1

200

250

300


100

260.2

Phenobarbital, di-ethyl derivative C16H20N2O3 MW: 288.34

50

146.1

O H 2C

H 3C

117.1

IV-2-B-i

C 2H 5 O N

N C 2H 5

O

103.1

202.1

232.1

273.2 288.2


100

100

150

200

300 261.2

Phenobarbital-d5, di-ethyl derivative 151.1

C16H15D5N2O3 MW: 293.37

50

250

105.1

O D 2C

D 3C

C 2H 5 O N N C 2H 5

O

122.1

IV-2-B-ii

204.1

233.1

275.2

293.2


100

100

150

200

Phenobarbital-d5, di-ethyl derivative C16H15D5N2O3 MW: 293.37

50

151.1 108.1

H 3C

D

O H 2C

122.1

C 2H 5 O N

D

IV-2-B-iii

300 265.2

N DO

D

250

D

C 2H 5

207.2

237.2

278.2

293.2

0 50

100

150

200 m/z



250

300

258


Relative Int. (%)

100

Phenobarbital, di-propyl derivative

H 3C

C18H24N2O3 MW: 316.39

50

146.1

C 3H 7 O N O H 2C N

117.1

288.2

IV-2-C-i

C 3H 7

O

246.1

204.1

103.1

275.2

174.1

316.2


100

100

150

200 151.1

Phenobarbital-d5, di-propyl derivative C18H19D5N2O3 MW: 321.42

50

D 3C

105.1

122.1

C 3H 7 O N O D 2C N C 3H 7 O

250

300

IV-2-C-ii

289.2

247.1

205.1

179.2

350

280.2

321.3


100

100

150

Phenobarbital-d5, di-propyl derivative

151.1 H 3C

C18H19D5N2O3 MW: 321.42

50

200

122.1

D

179.1 D

300

IV-2-C-iii

N C 3H 7

DO

251.2

209.1

D

280.2

321.3

0 50

Relative Int. (%)

100

100

150

C20H28N2O3 MW: 344.44

50

91.1

200 m/z

250

146.1

Phenobarbital, di-butyl derivative

C 4H 9 O N

O H 2C

H 3C

117.1

174.1

300

IV-2-D-i

289.2

350

316.2

N C 4H 9

O

103.1

350

293.2

C 3H 7 O N

O H 2C

D

108.1

250

189.1

260.2

233.1

344.3


100

100

150

C20H23D5N2O3 MW: 349.47 105.1

250

151.1

Phenobarbital-d5, di-butyl derivative

50

200 C 4H 9 O N

O D 2C

D 3C

122.2

179.2

IV-2-D-ii

350

294.2

N C 4H 9

O

91.1

300

194.2

317.2 261.2

234.2

349.3


100

100

150

Phenobarbital-d5, di-butyl derivative C20H23D5N2O3 MW: 349.47

50

96.1

200

250

151.1 H 3C

122.1

D

O H 2C

179.2

194.2

D

300

IV-2-D-iii

294.2

100

150

D

200 m/z



321.3

C 4H 9

238.2

265.2 349.3

0 50

350

N DO

D

108.1

C 4H 9 O N

250

300

350

259


Relative Int. (%)

100

Phenobarbital, di-trimethylsilyl derivative

146.0 H 3C

C18H28N2O3Si2 MW: 376.60

50

O H 2C

Si(CH3)3 O

IV-2-E-i

N

N Si(CH3)3

O

361.1

117.0

73.0

261.1

289.1


100

100

150

200 151.1

Phenobarbital-d5, di-trimethylsilyl derivative

73.0

O D 2C

D 3C

C18H23D5N2O3Si2 MW: 381.63

50

250

300

Si(CH3)3 O

376.2

347.1

0

350

400

IV-2-E-ii

N

N

366.2

Si(CH3)3

O

266.1

122.1

294.1

347.1

381.2


100

100

150

200 151.1

Phenobarbital-d5, di-trimethylsilyl derivative

H 3C

C18H23D5N2O3Si2 MW: 381.63

50

250

D

O H 2C

73.0

122.1

Si(CH3)3 O N

D

350

400

IV-2-E-iii

N DO

D

300

366.2

Si(CH3)3

266.1

D

294.1

352.1

381.2

0 50

100

150

200

250

300

350

400


100

Phenobarbital, di-t-butyldimethylsilyl derivative H 3C

C24H40N2O3Si2 MW: 460.75

50

O H 2C

100.0

IV-2-F-i

N Si(CH3)2C(CH3)3

O

73.1

403.2

Si(CH3)2C(CH3)3 O N

445.2

317.1

147.1

460.3

0 50

100

Relative Int. (%)

100

150

200

250

Phenobarbital-d5, di-t-butyldimethylsilyl derivative

50

73.1

O D 2C

D 3C

C24H35D5N2O3Si2 MW: 465.78

300

350

400

450

500

408.2

Si(CH3)2C(CH3)3 O N

IV-2-F-ii

N Si(CH3)2C(CH3)3

O

100.0

450.3

317.1

147.1

465.3

0 50

100

Relative Int. (%)

100

150

200

250

Phenobarbital-d5, di-t-butyldimethylsilyl derivative

50

73.1

C24H35D5N2O3Si2 MW: 465.78 100.0

H 3C

D

O H 2C

D

147.1

350

Si(CH3)2C(CH3)3 O

400

450

500

408.2

IV-2-F-iii

N

N DO

D

300

Si(CH3)2C(CH3)3

D

450.3

322.1

465.3

0 50

100

150

200

250

300 m/z



350

400

450

500

260

Figure IV-3. Mass spectra of butabital and its deuterated analogs (butabital-d5, -13C4): (A) underivatized; (B) [methyl]2derivatized; (C) [ethyl]2-derivatized; (D) [propyl]2-derivatized; (E) [butyl]2-derivatized; (F) [TMS]2-derivatized; (G) [t-BDMS]2-derivatized.

Relative Int. (%)

100

168.0

H O H 2C

50

HC HC

H 2C H 2C

H 3C CH 3

53.1

67.1

N

Butalbital (CAS NO.77-26-9)

IV-3-A-i

O

C11H16N2O3 MW: 224.25

N

H

O

124.0

97.0

181.0

141.0 153.0

0 50

100

Relative Int. (%)

100

150

200 173.1

H O DC D 2C HC H 2C H 3C CH 3

D 2C

50

C11H11D5N2O3 MW: 229.28

N H

O

129.0

100.1 55.1

Butalbital-d5 (CAS NO.125-40-6)

IV-3-A-ii

O

N

250

70.0

186.0

141.0

156.0

0 50

100

Relative Int. (%)

100

150 H

O HC H 2C HC H 2C H 3C CH 3

68.1

Butalbital-13C4 C713C4H16N2O3 MW: 228.22

* * ** N

H 2C

50

250

172.1

IV-3-A-iii

O

N

200

H

O

13 99.1 * = C

127.1

145.0

185.1

157.0

213.1

0 50

100

Relative Int. (%)

100 O H 2C

50

HC HC

H 2C H 2C

H 3C CH 3

150 m/z CH 3 O N

Butalbital, di-methyl derivative C13H20N2O3 MW: 252.30

N CH 3

O

181.0 138.0

169.0

209.1 237.1

0 50

100

150

200

Relative Int. (%)

100 O

DC D 2C HC H 2C H 3C CH 3

58.1

250

C13H15D5N2O3 MW: 257.34

N O

CH 3

143.1

116.1

300 Butalbital-d5, di-methyl derivative

201.1

IV-3-B-ii

CH 3 O N

D 2C

50

250

196.1

IV-3-B-i

111.1

58.1

200

169.0

184.1

214.1

242.1

0 50

100

150

Relative Int. (%)

100 O

HC H 2C HC H 2C H 3C CH 3

H 2C

50 68.1

CH 3 O

200 200.1

IV-3-B-iii

N

O

141.1

86.0

100

185.1 213.1

173.1

241.1

150

200 m/z



C913C4H20N2O3 MW: 256.28

CH 3

* = 13C 113.1

300 Butalbital-13C4, di-methyl derivative

* * ** N

0 50

250

250

300

261


Relative Int. (%)

100

224.2 C 2H 5 O N

O H 2C


50

C15H24N2O3 MW: 280.36

N C 2H 5

O

95.1

67.1

Butalbital, di-ethyl derivative

IV-3-C-i 196.1

125.1

109.1

168.1

209.1

237.2

265.2 280.2

0 50

100

150

200

250

Relative Int. (%)

100 C 2H 5 O N

O DC D 2C HC H 2C H 3C CH 3

D 2C

50

Butalbital-d5, di-ethyl derivative

IV-3-C-ii

C15H19D5N2O3 MW: 285.39

N C 2H 5

O

201.1

100.1 113.1

70.1

300

229.2

130.1

171.1

212.1

242.2

270.2

0 50

100

150

200

250

Relative Int. (%)

100 HC H 2C HC H 2C H 3C CH 3

68.1

Butalbital-13C4, di-ethyl derivative

IV-3-C-iii

* * ** N

H 2C

50

300

228.1

C 2H 5 O N

O

97.1

C1113C4H24N2O3 MW: 284.33

C 2H 5

O

200.1 213.1

127.1

* = 13C

155.0

241.1

172.0

269.1 284.2

0 50

285.2

100

150

200

250

300


100

IV-3-D-i

O

H 2C


50

N C 3H 7

O

95.1

67.1

Butalbital, di-propyl derivative

252.2

C 3H 7 O N

138.1

C17H28N2O3 MW: 308.41

210.1

168.1 180.1

265.2 235.2

293.2

308.3

0 50

100

150

Relative Int. (%)

100

IV-3-D-ii

O


50

300

C17H23D5N2O3 MW: 313.44

C 3H 7

O

270.2 185.2

143.1

350

Butalbital-d5, di-propyl derivative

215.2

173.1

N

100.1

72.1

250 257.2

C 3H 7 O N

D 2C

200

240.2

298.3

313.3


100

100

150

IV-3-D-iii H 2C

50 68.1

O HC HC

H 2C H 2C

H 3C CH 3

97.1

200

250

C 3H 7 O N

256.1

* * ** N

O

300

172.0

Butalbital-13C4, di-propyl derivative

214.1

C1313C4H28N2O3 MW: 312.39

C 3H 7

* = 13C 141.1

183.1

350

269.1

229.1

297.2

312.2

0 50

100

150

200 m/z



250

300

350

262


Relative Int. (%)

100 H 2C

50

HC HC

H 2C H 2C

IV-3-E-i

Butalbital, di-butyl derivative 279.2

C19H32N2O3 MW: 336.46

N C 4H 9

O

H 3C CH 3

182.1 207.2

168.1

138.1

95.1

67.1

263.2

C 4H 9 O N

O

293.2

224.2

321.3 336.3

0 50

100

150

Relative Int. (%)

100 D 2C


300

350 Butalbital-d5, di-butyl derivative

IV-3-E-ii

C19H27D5N2O3 MW: 341.49

N

C 4H 9

O

285.3 187.1 212.2

173.1

100.1

72.1

250 268.3

C 4H 9 O N

O

50

200

298.3

229.2

143.1

326.3

341.3

0 50

100

150

200

250

300

Relative Int. (%)

100 O H 2C

50 68.1

HC HC

H 2C H 2C

C 4H 9 O N

267.2

IV-3-E-iii

4, di-butyl derivative

283.1

* * ** N

H 3C CH 3

O

C 4H 9

172.1

186.1

297.2

228.1

211.1

* = 13C

350 Butalbital-13C

C1513C4H32N2O3 MW: 340.43 325.2 340.2

0 50

Relative Int. (%)

100

100

150

200 m/z

Butalbital, di-trimethylsilyl derivative

O

73.0

100.0


Si(CH3)3 O N

H 2C

C17H32N2O3Si2 MW: 368.62

50

147.0

250

300

353.2

IV-3-F-i

N

312.1 325.1

Si(CH3)3

O

297.1 269.0

210.1

368.2


100

100

150

200

Butalbital-d5, di-trimethylsilyl derivative

O

C17H27D5N2O3Si2 MW: 373.65

50

73.0

100.0


250 Si(CH3)3 O N

D 2C

147.0

300

400 358.2

317.1

Si(CH3)3

215.1

350

IV-3-F-ii

N O

350

330.2

269.0

302.1 373.2


100

100

150

200

Butalbital-13C4, di-trimethylsilyl derivative C1313C4H32N2O3Si2 MW: 372.58 73.1 101.1

50

O H 2C

147.1


250

300

* * ** N

316.2 Si(CH3)3

* = 13C

301.1

329.2

273.1

372.2

0 50

100

150

200

250 m/z



400 357.2

IV-3-F-iii

Si(CH3)3 O N

O

350

300

350

400

263


Relative Int. (%)

100

C23H44N2O3Si2 MW: 452.77

50

73.1

50

100

O

H 2C

HC HC

H 2C H 2C

H 3C CH 3

100.1

0

Relative Int. (%)

395.3

Butalbital, di-t-butyldimethylsilyl derivative

100

200

250

100.1

300

452.3

350

400

450


N Si(CH3)2C(CH3)3

O

442.3

297.1

457.4


100

100

150

200

250

Butalbital-13C

4, di-t-butyldimethylsilyl derivative

C1913C4H44N2O3Si2 MW: 456.74

50

73.1

O H 2C

HC HC

H 2C H 2C

H 3C CH 3

101.1

300

350

400 399.3

Si(CH3)2C(CH3)3 O N

450

100

* * ** N

O

Si(CH3)2C(CH3)3

* = 13C

147.1

150

200

441.3

301.2

250

300 m/z



500

IV-3-G-iii

357.2

456.3

0 50

500

IV-3-G-ii

Si(CH3)2C(CH3)3 O N

D 2C

147.1

437.3

400.3 O

C23H39D5N2O3Si2 MW: 457.80 73.1

Si(CH3)2C(CH3)3

297.1

Butalbital-d5, di-t-butyldimethylsilyl derivative

50

N

O

147.1

150

IV-3-G-i

Si(CH3)2C(CH3)3 O N

350

400

450

500

264

Figure IV-4. Mass spectra of secobarbital and its deuterated analogs (secobarbital-d5, -13C4): (A) underivatized; (B) [methyl]2-derivatized; (C) [ethyl]2-derivatized; (D) [propyl]2-derivatized; (E) [butyl]2-derivatized; (F) [TMS]2derivatized; (G) [t-BDMS]2-derivatized.

Relative Int. (%)

100

IV-4-A-i

50

168.0

H

C12H18N2O3 MW: 238.28

N H 2C HC H 2C N H 2C H 2C HC H O CH 3

H 3C

124.0

53.1

Secobarbital (CAS NO.76-73-3)

O

O

195.1

153.0

79.1

223.1


100

100

150 H O N DC D 2C

IV-4-A-ii D 2C

H 2C

H 3C

50

HC

H 2C

173.0

250

O

C12H13D5N2O3 MW: 243.31

N

H

O

CH 3

102.1 55.0

200

Secobarbital-d5 (CAS NO.145243-97-6)

129.0

200.1

155.0

83.1

0 50

100

150

Relative Int. (%)

100

200

H O

IV-4-A-iii

H 2C

H 3C

50

H 2C

HC

H 2C

H 2C

HC

*=

55.1

O

C813C4H18N2O3 MW: 242.26

* * ** N

CH 3

13C

N

250 Secobarbital-13C4

172.1

O

H

127.0

199.1

157.0

80.1

227.1

0 50

100

Relative Int. (%)

100 O

H 3C

50

150 m/z

CH 3 O

200

196.0

IV-4-B-i

N

H 2C HC H 2C N H 2C H 2C HC CH 3 O CH 3

250

Secobarbital, di-methyl derivative C14H22N2O3 MW: 266.33

181.0 138.0

111.0

223.0 237.1

58.0

266.1

0 50

100

Relative Int. (%)

100 O H 3C

50

150 CH 3 O N

250 201.1

IV-4-B-ii

D 2C DC D 2C N H 2C H 2C HC CH 3 O CH 3

300 Secobarbital-d5, di-methyl derivative C14H17D5N2O3 MW: 271.37

183.0

116.1

58.0

200

228.1 242.1

143.0

271.2

0 50

100

150

Relative Int. (%)

100

CH 3 O

O H 2C H 3C

50

H 2C

HC

H 2C

H 2C

HC

* * ** N

CH 3

* = 13C

54.1

N

O

200 200.1

C1013C4H22N2O3 MW: 270.31

185.1 141.1

223.1

252.1 270.1

227.1

173.1

0 50

100

150

200 m/z



300 Secobarbital-13C4, di-methyl derivative

IV-4-B-iii

CH 3

113.1

250

250

300

265


Relative Int. (%)

100

C 2H 5 O N

O

H 2C HC H 2C N H 2C H 2C HC C 2H 5 O CH 3

H 3C

50

224.2

IV-4-C-i

81.1

C16H26N2O3 MW: 294.38 209.1

125.1

109.1

Secobarbital, di-ethyl derivative

196.1

152.1

294.3

265.2

237.2

0 50

100

150

Relative Int. (%)

100

130.1

113.1

86.1

300 Secobarbital-d5, di-ethyl derivative

229.2

C16H21D5N2O3 MW: 299.41

D 2C DC D 2C N H 2C H 2C HC C 2H 5 O CH 3

H 3C

50

250

IV-4-C-ii

C 2H 5 O N

O

200

201.1

157.1

212.1

270.2

237.2

299.3

0 50

100

150

Relative Int. (%)

100 O H 3C

50

Pentobarbital-13C4, di-ethyl derivative C1213C4H26N2O3 MW: 298.35

127.1

200.1 155.1

213.1

172.1

100

150

269.1

200.1

0 50

300

C 2H 5

112.0

71.1

250 228.1

IV-4-C-iii

* * ** N

H 2C HC H 2C H 2C H 2C HC O CH 3 * = 13C

200 m/z

C 2H 5 O N

200

298.2

250

300


100 O

H 3C

50

C 3H 7 O N

252.2

IV-4-D-i


C18H30N2O3 MW: 322.44

210.1 168.1

124.1

81.1

Secobarbital, di-propyl derivative

293.2

237.2

322.3

0 50

100

150

Relative Int. (%)

100 O H 3C

50

C 3H 7 O N

200

300 257.2

IV-4-D-ii


350

Secobarbital-d5, di-propyl derivative C18H25D5N2O3 MW: 327.47

215.2

173.1

298.3

240.2

129.1

86.1

250

327.3

0 50

100

150

Relative Int. (%)

100 O

50

H 3C

57.1

C 3H 7 O N

H 2C HC H 2C ** * * N H 2C H 2C HC C 3H 7 O 13 CH *= C 3

82.1

200 m/z

250

300 256.1

IV-4-D-iii

Secobarbital-13C4, di-propyl derivative C1413C4H30N2O3 MW: 326.41

214.1

172.0

127.0

297.1

241.1

0 50

100

150

200 m/z



350

250

300

326.2

350

266


Relative Int. (%)

100 O

H 3C

50

279.2

C 4H 9 O N

IV-4-E-i


109.1

Secobarbital, di-butyl derivative

263.2

C20H34N2O3 MW: 350.49

168.1

224.2

207.1

81.1

321.3

309.3

350.3

0 50

100

150

Relative Int. (%)

100 O H 3C

50

200

IV-4-E-ii


86.1

300

350

400

Secobarbital-d5, di-butyl derivative

268.3

C 4H 9 O N

285.3

C20H29D5N2O3 MW: 355.53 229.2

212.2

173.1

114.1

250

326.3

309.3

355.4

0 50

100

150

Relative Int. (%)

100 O H 3C

50

200

300

350

283.2

4, di-butyl derivative

C1613C4H34N2O3 MW: 354.46

C 4H 9

228.1

186.1

172.1

400

Secobarbital-13C

267.2

IV-4-E-iii

* * ** N

H 2C HC H 2C H 2C H 2C HC O CH 3 * = 13C

250 m/z

C 4H 9 O N

325.2

313.2

83.1

354.3

0 50

100

150

200

250

300

350

400


100

Secobarbital, di-trimethylsilyl derivative C18H24N2O3Si2 MW: 382.64

50 73.1

100.0

109.0

IV-4-F-i H 3C

147.0

297.1

Si(CH3)3 O N

O


182.0

312.1

339.1

367.2

281.1

225.0

0 50

100

Relative Int. (%)

100

150

200

Secobarbital-d5, di-trimethylsilyl derivative

50 73.1

IV-4-F-ii

C18H19D5N2O3Si2 H 3C MW: 387.67 100.0 147.0 114.1

250

D 2C DC D 2C H 2C H 2C HC

100

Relative Int. (%)

100

150

50 73.1

IV-4-F-iii

C1413C4H24N2O3Si2 H 3C MW: 386.91 101.1 147.1 111.1

344.2

CH 3

O

286.1

230.1

200

Secobarbital-13C4, di-trimethylsilyl derivative

400 372.2

317.2

N

CH 3

0 50

350 302.1

Si(CH3)3 O N

O

187.1

300

250 O

300

H 2C

229.1

185.1

400

301.2

Si(CH3)3 O N

HC H 2C ** * * N H 2C H 2C HC CH 3 O 13 CH *= C 3

350

316.2

371.2 343.2

285.1

0 50

100

150

200

250 m/z



300

350

400

267


Relative Int. (%)

100

Secobarbital, di-t-butyldimethylsilyl derivative

50

C24H46N2O3Si2 MW: 466.80 73.1 100.1

O

H 3C

Si(CH3)2C(CH3)3 O N


281.1

409.3

IV-4-G-i 339.2

311.1

451.3

381.2


100

100

150

200

Secobarbital-d5, di-t-butyldimethylsilyl derivative

50

C24H41D5N2O3Si2 MW: 471.83 73.1 100.1

250

Si(CH3)2C(CH3)3 O N

O H 3C

300

D 2C DC D 2C N H 2C H 2C HC CH 3 O CH 3

350


100

200

Secobarbital-13C4, di-t-butyldimethylsilyl derivative

50

C2013C4H46N2O3Si2 MW: 471.07 73.1 101.1

250

H 2C H 3C

H 2C

HC

H 2C

H 2C

HC

* = 13C

300 Si(CH3)2C(CH3)3 O N

O

* * ** N

O

500

344.2

286.1 311.1

150

450 414.3

IV-4-G-ii

456.3

386.2

0 100

400

350

400

450

500

413.3

IV-4-G-iii 343.2

CH 3

CH 3

285.1

315.2

455.3

385.2

0 50

100

150

200

250

300 m/z



350

400

450

500

268

Figure IV-5. Mass spectra of methohexital and its deuterated analogs (methohexital-d5): (A) underivatized; (B) methylderivatized; (C) ethyl-derivatized; (D) propyl-derivatized; (E) butyl-derivatized; (F) TMS-derivatized; (G) t-BDMSderivatized. Relative Int. (%)

100

79.0

O

53.0

50 65.0

93.0

H 3C

CH 3 O

H 2C HC H 2C H 2C C C HC

108.1 120.1

N H 164.0

O CH 3

221.0

IV-5-A-i

N

Methohexital (CAS NO.151-83-7) 233.0

178.0

C14H18N2O3 MW: 262.30

247.1

261.1

205.0

0 50

100

150

200

Relative Int. (%)

100 79.0 O

53.0

50

H 3C

65.0

96.1

111.1 124.1

164.0

N

221.0

IV-5-A-ii

CH 3 O N

D 2C DC D 2C H 2C C C HC

250

Methohexital-d5 (CAS NO.160227-45-2) C14H13D5N2O3 MW: 267.33

178.0 252.1

238.1

H

O CH 3

300

266.1

209.1

0 50

100

150

200

250

300


100 O

79.0

50

H 3C

53.0


93.0 120.0

138.0

235.0

CH 3 O N

178.0

247.0 261.1

N

195.0

CH 3

O CH 3

Methohexital, methyl derivative

IV-5-B-i

C15H20N2O3 MW: 276.33 275.1

219.1

0 50

100

150

Relative Int. (%)

100 O

79.0

50 53.0

H 3C

96.0

200


178.0

CH 3

266.1

200.1

143.0

300 Methohexital-d5, methyl derivative

IV-5-B-ii

N

O CH 3

124.1

250 235.1

CH 3 O N

C15H15D5N2O3 MW: 281.36

252.1 223.1

280.1

0 50

100

150

200

250

300


100 O

50

79.1 53.1

H 3C

91.1


Methohexital, ethyl derivative

IV-5-C-i

N

178.1

C 2H 5

O CH 3

120.1

249.2

CH 3 O

N

209.1 194.1

261.2 233.2

161.1

138.1

C16H22N2O3 275.2 MW: 290.36 290.2

0 50

100

150

Relative Int. (%)

100 O

50

79.1 53.1

H 3C

96.1


124.1

200

CH 3 O N

250

IV-5-C-ii

249.2

Methohexital-d5, ethyl derivative C16H17D5N2O3 MW: 295.39

N

O CH 3

143.1

C 2H 5

178.1

164.1

300

196.1

214.2

280.2 238.2

266.2

295.3

0 50

100

150

200 m/z



250

300

269


Relative Int. (%)

100 O

50


H 3C

79.1

CH 3 O

53.1

Methohexital, propyl derivative C17H24N2O3 MW: 304.38

N C 3H 7

O CH 3

105.1

263.2

IV-5-D-i

N

178.1

223.2 197.1

138.1

289.2

275.2 247.2

303.2

0 50

100

150

Relative Int. (%)

100 O

50

79.1

CH 3 O N


H 3C

200

114.1

300 263.2

IV-5-D-ii

350 Methohexital-d5, propyl derivative C17H19D5N2O3 MW: 309.41

N C 3H 7

O CH 3

53.1

250

178.1 294.2

221.1 187.1

143.1

280.2

252.2

309.3

0 50

100

150

Relative Int. (%)

100 O

50

79.1 53.1

CH 3 O N


H 3C

200 m/z

93.1

120.1

300

C 4H 9

221.1 237.2

178.1

161.1

211.1

150

200

350

277.2

IV-5-E-i

N

O CH 3

250

Methohexital, butyl derivative C18H26N2O3 MW: 318.41

303.2

289.2 318.2

0 50

100

Relative Int. (%)

100 O H 3C

50 79.1 53.1

CH 3 O

124.1

350 Methohexital-d5, butyl derivative

N

O CH 3

96.1

300 277.2

IV-5-E-ii

N


250

C 4H 9

178.1

164.1

308.3

221.1 242.2

214.2

C18H21D5N2O3 MW: 323.44

294.2

323.3

0 50

100

150

200 m/z

Relative Int. (%)

100

IV-5-F-i

O H 3C

50 73.0

300

239.1

CH 3 O N


350

Methohexital, trimethylsilyl derivative

N Si(CH3)3

O CH 3

100.0

250

178.0

319.1

264.1

211.0

138.0

C17H26N2O3Si MW: 334.48

293.1

333.1

0 50

100

150

200

Relative Int. (%)

100

IV-5-F-ii

O H 3C

50 73.0


300

244.1

CH 3 O N

O CH 3

100.0

250

Methohexital-d5, trimethylsilyl derivative

N

C17H21D5N2O3Si MW: 339.51 324.1 339.2

293.1

Si(CH3)3

178.0 269.2

213.0

143.0

350

0 50

100

150

200 m/z



250

300

350

270


Relative Int. (%)

100

IV-5-G-i 50

H 3C

75.1

O

239.1

CH 3 O N


319.2

N

Methohexital, t-butyldimethylsilyl derivative C20H32N2O3Si MW: 376.56

Si(CH3)2C(CH3)3

O CH 3

100.1

211.1

361.2

281.1


100

100

IV-5-G-ii H 3C

50

73.1

150 O


200

250

300

244.1

CH 3 O

N

324.2

N

O CH 3

Si(CH3)2C(CH3)3

100.1

213.1

286.2

0 50

100

150

200

250 m/z



350

300

376.2

400

Methohexital-d5, t-butyldimethylsilyl derivative C20H27D5N2O3Si MW: 381.60 366.2 381.3

350

400

271

Figure IV-6. Mass spectra of γ-hydroxybutyric acid (GHB) and its deuterated analogs (GHB-d6): (A) [TMS]2derivatized; (B) [t-BDMS]2-derivatized.

Relative Int. (%)

100

γ-Hydroxybutyric acid (CAS NO.591-81-1), di-trimethylsilyl derivative

147.1

IV-6-A-i

O 3(H3C)SiO-CH2-CH2-CH2-C-OSi(CH3)3

50

C10H24O3Si2 MW: 248.47

233.1 73.1

117.1

204.1

0 50

100

150

Relative Int. (%)

100

200

250

147.1

IV-6-A-ii

O 3(H3C)SiO-CD2-CD2-CD2-C-OSi(CH3)3

300

γ-Hydroxybutyric acid-d6, di-trimethylsilyl derivative C10H18D6O3Si2 MW: 254.50

50 239.1 73.1

206.1

121.1

0 50

100

150

200

250

300


100

IV-6-B-i

147.1 275.1 O

73.1

50

(H3C)3C(H3C)2SiO-CH2-CH2-CH2-C-OSi(CH3)2C(CH3)3

C16H36O3Si2 MW: 332.62

133.0

317.2

201.1

0 50

100


γ-Hydroxybutyric acid, di-t-butyldimethylsilyl derivative

150

IV-6-B-ii

200

250

300

γ-Hydroxybutyric acid-d6, di-t-butyldimethylsilyl derivative

(H3C)3C(H3C)2SiO-CD2-CD2-CD2-C-OSi(CH3)2C(CH3)3

C16H30D6O3Si2 MW: 338.65

O

50

73.1

350

281.2

147.1

133.0 323.2

207.1

0 50

100

150

200 m/z



250

300

350

272

Figure IV-7. Mass spectra of γ-butyrolactone (GBL) and its deuterated analogs (GBL-d6).

Relative Int. (%)

100

γ-Butyrolactone (CAS NO.94-48-0) O

C4H6O2 MW: 86.09

50

IV-7-i

86.1

O

56.1 85.1 55.1


100

100 γ-Butyrolactone-d6 C4D6O2 MW: 92.13

50

60.1

D O O D D D D D

92.1

IV-7-ii

90.1

58.1

0 50

100 m/z



273

Summary of Drugs, Isotopic Analogs, and Chemical Derivatization Groups Included in Figure V (Antianxiety Agents) Compound

Isotopic analog


Figure #

Oxazepam

d5

None, [methyl]2, [ethyl]2, [propyl]2, [butyl]2, [TMS]2, t-BDMS (14)

V-1

Diazepam

d3, d5

None (3)

V-2

Nordiazepam

d5

None, methyl, ethyl, propyl, butyl, TMS, t-BDMS (14)

V-3

Nitrazepam

d5

Methyl, ethyl, propyl, butyl, TMS, t-BDMS (12)

V-4

Temazepam

d5

None, methyl, ethyl, propyl, butyl, acetyl, TMS, t-BDMS (16)

V-5

Clonazepam

d4

Methyl, ethyl, propyl, butyl, TMS, t-BDMS (12)

V-6

7-Aminoclonazepam

d4

[Methyl]3, [ethyl]2, [ethyl]3, propyl, [propyl]2, butyl, [butyl]2, PFP, HFB, [TMS]2, t-BDMS, [t-BDMS]2, TFA/[TMS]2, [TFA]2/t-BDMS, TFA/[t-BDMS]2, PFP/TMS, PFP/[TMS]2, PFP/[t-BDMS]2, HFB/[t-BDMS]2 (38)

V-7

Prazepam

d5

None (2)

V-8

Lorazepam

d4

[Methyl]2, [ethyl]2, [propyl]2, [butyl]2, HFB, [TMS]2, [t-BDMS]2 (14)

V-9

Flunitrazepam

d3, d7

None (3)

V-10

7-Aminoflunitrazepam

d3, d7

None, [methyl]2, ethyl, [ethyl]2, propyl, butyl, acetyl, TFA, PFP, HFB, TMS, TFA/TMS, TFA/t-BDMS, PFP/TMS, PFP/t-BDMS, HFB/TMS, HFB/t-BDMS (51)

V-11

N-Desalkylflurazepam

d4

None, methyl, [methyl]2, ethyl, propyl, butyl, acetyl, TMS,, t-BDMS (18)

V-12

N-Desmethylflunitrazepam

d4

[Methyl]2, ethyl, propyl, butyl, acetyl, TMS, t-BDMS (14)

V-13

2-Hydroxyethylflurazepam

d4

None, butyl, TMS, t-BDMS (8)

V-14

Estazolam

d5

None (2)

V-15

Alprazolam

d5

None (2)

V-16

α-Hydroxyalprazolam

d5

TMS, t-BDMS (4)

V-17

α-Hydroxytriazolam

d4

TMS, t-BDMS (4)

V-18

Mianserin

d3

None (2)

V-19

Methaqualone

d7

None (2)

V-20

Haloperidol

d4

TMS (2)

V-21


Figure V — Antianxiety Agent


275

Appendix One — Figure V Mass Spectra of Commonly Abused Drugs and Their Isotopically Labeled Analogs in Various Derivatization Forms — Antianxiety Agents Figure V-1. Mass spectra of oxazepam and its deuterated analogs (oxazepam-d5): (A) underivatized; (B) [methyl]2derivatized; (C) [ethyl]2-derivatized; (D) [propyl]2-derivatized; (E) [butyl]2-derivatized; (F) [TMS]2-derivatized; (G) [tBDMS]2-derivatized ...................................................................................................................................................................... 276 Figure V-2. Mass spectra of diazepam and its deuterated analogs (diazepam-d3, -d5) ............................................................... 279 Figure V-3. Mass spectra of nordiazepam and its deuterated analogs (nordiazepam-d5): (A) underivatized; (B) methylderivatized; (C) ethyl-derivatized; (D) propyl-derivatized; (E) butyl-derivatized; (F) TMS-derivatized; (G) t-BDMSderivatized ..................................................................................................................................................................................... 280 Figure V-4. Mass spectra of nitrazepam and its deuterated analogs (nitrazepam-d5): (A) methyl-derivatized; (B) ethylderivatized; (C) propyl-derivatized; (D) butyl-derivatized; (E) TMS-derivatized; (F) t-BDMS-derivatized ............................. 283 Figure V-5. Mass spectra of temazepam and its deuterated analogs (temazepam-d5): (A) underivatized; (B) methylderivatized; (C) ethyl-derivatized; (D) propyl-derivatized; (E) butyl-derivatized; (F) acetyl-derivatized; (G) TMS-derivatized; (H) t-BDMS-derivatized .............................................................................................................................................................. 285 Figure V-6. Mass spectra of clonazepam and its deuterated analogs (clonazepam-d4): (A) methyl-derivatized; (B) ethylderivatized; (C) propyl-derivatized; (D) butyl-derivatized; (E) TMS-derivatized; (F) t-BDMS-derivatized ............................. 288 Figure V-7. Mass spectra of 7-aminoclonazepam and its deuterated analogs (7-aminoclonazepam-d4): (A) [methyl]3derivatized; (B) [ethyl]2-derivatized; (C) [ethyl]3-derivatized; (D) propyl-derivatized; (E) [propyl]2-derivatized; (F) butylderivatized; (G) [butyl]2-derivatized; (H) PFP-derivatized; (I) HFB-derivatized; (J) [TMS]2-derivatized; (K) t-BDMSderivatized; (L) [t-BDMS]2-derivatized; (M) TFA/[TMS]2-derivatized; (N) [TFA]2/t-BDMS-derivatized; (O) TFA/[tBDMS]2-derivatized; (P) PFP/TMS-derivatized; (Q) PFP/[TMS]2-derivatized; (R) PFP/[t-BDMS]2-derivatized; (S) HFB/ [t-BDMS]2-derivatized .................................................................................................................................................................. 290 Figure V-8. Mass spectra of prazepam and its deuterated analogs (prazepam-d5) ..................................................................... 297 Figure V-9. Mass spectra of lorazepam and its deuterated analogs (lorazepam-d4): (A) [methyl]2-derivatized; (B) [ethyl]2derivatized; (C) [propyl]2-derivatized; (D) [butyl]2-derivatized; (E) HFB-derivatized; (F) [TMS]2-derivatized; (G) [tBDMS]2-derivatized ...................................................................................................................................................................... 298 Figure V-10. Mass spectra of flunitrazepam and its deuterated analogs (flunitrazepam-d3, -d7) ............................................... 301 Figure V-11. Mass spectra of 7-aminoflunitrazepam and its deuterated analogs (7-aminoflunitrazepam-d3, -d7): (A) underivatized; (B) [methyl]2-derivatized; (C) ethyl-derivatized; (D) [ethyl]2-derivatized; (E) propyl-derivatized; (F) butylderivatized; (G) acetyl-derivatized; (H) TFA-derivatized; (I) PFP-derivatized; (J) HFB-derivatized; (K) TMS-derivatized; (L) TFA/TMS-derivatized; (M) TFA/t-BDMS-derivatized; (N) PFP/TMS-derivatized; (O) PFP/t-BDMS-derivatized; (P) HFB/TMS-derivatized; (Q) HFB/t-BDMS-derivatized .............................................................................................................. 302 Figure V-12. Mass spectra of N-desalkylflurazepam and its deuterated analogs (N-desalkylflurazepam-d4): (A) underivatized; (B) methyl-derivatized; (C) [methyl]2-derivatized; (D) ethyl-derivatized; (E) propyl-derivatized; (F) butyl-derivatized; (G) acetyl-derivatized; (H) TMS-derivatized; (I) t-BDMS-derivatized ............................................................................................. 311 Figure V-13. Mass spectra of N-desmethylflunitrazepam and its deuterated analogs (N-desmethylflunitrazepam-d4): (A) [methyl]2-derivatized; (B) ethyl-derivatized; (C) propyl-derivatized; (D) butyl-derivatized; (E) acetyl-derivatized; (F) TMS-derivatized; (G) t-BDMS-derivatized ................................................................................................................................. 314 Figure V-14. Mass spectra of 2-hydroxyethylflurazepam and its deuterated analogs (2-hydroxyethylflurazepam-d4): (A) underivatized; (B) butyl-derivatized; (C) TMS-derivatized; (D) t-BDMS-derivatized ............................................................... 317 Figure `V-15. Mass spectra of estazolam and its deuterated analogs (estazolam-d5) ................................................................. 319 Figure V-16. Mass spectra of alprazolam and its deuterated analogs (alprazolam-d5) .............................................................. 320 Figure V-17. Mass spectra of α-hydroxyalprazolam and its deuterated analogs (α-hydroxyalprazolam-d5): (A) TMSderivatized; (B) t-BDMS-derivatized ........................................................................................................................................... 321 Figure V-18. Mass spectra of α-hydroxytriazolam and its deuterated analogs (α-hydroxytriazolam-d4): (A) TMSderivatized; (B) t-BDMS-derivatized ........................................................................................................................................... 322 Figure V-19. Mass spectra of mianserin and its deuterated analogs (mianserin-d3) .................................................................. 323 Figure V-20. Mass spectra of methaqualone and its deuterated analogs (methaqualone-d7) ..................................................... 324 Figure V-21. Mass spectra of haloperidol and its deuterated analogs (haloperidol-d4): (A) TMS-derivatized ......................... 325



276

Figure V-1. Mass spectra of oxazepam and its deuterated analogs (oxazepam-d5): (A) underivatized; (B) [methyl]2derivatized; (C) [ethyl]2-derivatized; (D) [propyl]2-derivatized; (E) [butyl]2-derivatized; (F) [TMS]2-derivatized; (G) [t-BDMS]2-derivatized. Relative Int. (%)

100

V-1-A-i

C15H11ClN2O2 MW: 286.71

77.0

50

269.0

Cl

Oxazepam (CAS NO.604-75-1)

241.0

205.1

NH N

104.1

233.0

O

177.0

OH

136.0

0 50

100

Relative Int. (%)

100

150

Oxazepam-d5 (CAS NO.65854-78-6) C15H6D5ClN2O2 MW: 291.74

82.1

50

Cl

D

D

D

D

V-1-A-ii

D

109.1

54.1

200

250

300 274.0

246.0 210.1

NH N

O

OH

136.0

238.1 181.0

0 50

100

150

200

250

300


100

271.0 Cl

V-1-B-i 50

N N

77.1

Oxazepam, di-methyl derivative C17H15ClN2O2 MW: 314.77

255.0

CH 3

314.0

O O CH 3

0 50

100

150

Relative Int. (%)

100

200

250

300 276.0

Cl

V-1-B-ii

D

D

D

N CH 3 N D O O CH 3

D

50 82.1

350

Oxazepam-d5, di-methyl derivative C17H10D5ClN2O2 MW: 319.80

260.1

319.1

0 50

100

150

200 m/z

250

Relative Int. (%)

100

50

N N

77.0

350

Oxazepam, di-ethyl derivative

285.0

Cl

V-1-C-i

300

C19H19ClN2O2 MW: 342.82

C 2H 5

257.0

O O C 2H 5

241.0 342.1

0 50

100

150

Relative Int. (%)

100

200

D

82.1

350 Oxazepam-d5, di-ethyl derivative

D

D D

300 290.1

Cl

V-1-C-ii 50

250

D

N

C19H14D5ClN2O2 MW: 347.85

N C 2H 5

262.0

O O C 2H 5

246.0

347.1

0 50

100

150

200 m/z



250

300

350

277

Figure V-1. (Continued)

Relative Int. (%)

100

299.0

Cl

V-1-D-i 50

N N

77.0

Oxazepam, di-propyl derivative C21H23ClN2O2 MW: 370.87

257.0

C 3H 7

O O C 3H 7

241.0

370.1

328.0

0 50

100

150

Relative Int. (%)

100

250

300

D

D

D

N C 3H 7 N D O O C 3H 7

D

82.1

350

400

Oxazepam-d5, di-propyl derivative

304.1

Cl

V-1-D-ii 50

200

C21H18 D5ClN2O2 MW: 375.90

262.0 246.0

375.2

333.1

0 50

100

150

200

250

300

350

400


100

313.1

Oxazepam, di-butyl derivative

Cl

V-1-E-i 50

N N

57.1

O O C 4H 9

C23H27ClN2O2 MW: 398.93

257.0

C 4H 9

298.1

241.0

342.0

398.1

0 50

100

150

200

250

300

Relative Int. (%)

100

350

Cl

V-1-E-ii 50

D

D

D

N C 4H 9 N D O O C 4H 9

D

57.1

400

450

Oxazepam-d5, di-butyl derivative

318,1

C23H22D5ClN2O2 MW: 403.96

262.0

304.1

246.0

347.1

403.2

0 50

100

Relative Int. (%)

100

150

200

Oxazepam, di-trimethylsilyl derivative

250 m/z

350

Cl

73.1 C21H27ClN2O2Si2 MW: 431.08

50

300

147.1

450

429.1

V-1-F-i N

N

400

Si(CH3)3

313.0

O O Si(CH3)3

340.1

401.1


100

100

150

200

73.1 Oxazepam-d5, di-trimethylsilyl derivative C21H22D5ClN2O2Si2 MW: 436.11 147.1

50

250

300

350

Cl D

D

D

D

D N

400 433.1

V-1-F-ii N Si(CH3)3

318.1

O O Si(CH3)3

450

406.1 345.1

0 50

100

150

200

250 m/z



300

350

400

450

278


Relative Int. (%)

100 73.1

50

Oxazepam, di-t-butyldimethylsilyl derivative

Cl

V-1-G-i

Si(CH3)2C(CH3)3 O O Si(CH3)2C(CH3)3 N

N

147.1

457.1

C27H39ClN2O2Si2 MW: 515.23 383.1

313.0

513.2 499.2

0 50

100

150

200

250

300

350

Relative Int. (%)

100 73.1

50

D

D

D

D

D

147.1

N

450

N Si(CH3)2C(CH3)3 O O Si(CH3)2C(CH3)3

318.1

500

550

462.2

Oxazepam-d5, di-t-butyldimethylsilyl derivative

Cl

V-1-G-ii

400

C27H34D5ClN2O2Si2 MW: 520.26 387.1

519.3 504.2

0 50

100

150

200

250

300 m/z

350



400

450

500

550

279

Figure V-2. Mass spectra of diazepam and its deuterated analogs (diazepam-d3, -d5). Relative Int. (%)

100

Diazepam (CAS NO.439-14-5),

261.0

Cl

283.0

C16H13ClN2O MW: 284.74

50

V-2-i N

221.0

165.0

110.1

77.0

N CH 3 O


100

100

150

Diazepam-d3

200

250 259.0

Cl

C16H10D3ClN2O MW: 287.76

50

N

111.6

77.0

N CD 3

300 286.0

V-2-ii

O

224.0

167.0


100

100

150

Diazepam-d5 (CAS NO.65854-76-4), C16H8D5ClN2O MW: 289.77

50

Cl D

D

D

D

D

112.4

82.1

200

N

250

300

261.0

V-2-iii

287.0

N CH 3 O

226.1

170.1

0 50

100

150

200 m/z



250

300

280

Relative Int. (%)

Figure V-3. Mass spectra of nordiazepam and its deuterated analogs (nordiazepam-d5): (A) underivatized; (B) methylderivatized; (C) ethyl-derivatized; (D) propyl-derivatized; (E) butyl-derivatized; (F) TMS-derivatized; (G) t-BDMSderivatized. 100

Nordiazepam (CAS NO.1088-11-5)

242.0

Cl

C15H11ClN2O MW: 270.71

50

269.0

V-3-A-i NH

N

103.0

77.0

O

207.0

151.0


100

100

150

Nordiazepam-d5 (CAS NO.65891-80-7) C15H6D5ClN2O MW: 275.74

50

250

300

247.0

Cl

V-3-A-ii

D

D

D

N D

D

275.0

273.0

NH

105.5

78.1

200

O

155.0

212.1

0 50

100

150

200

250

300


100

Nordiazepam, methyl derivative C16H13ClN2O MW: 284.74

50

N

89.0

77.0

256.0

V-3-B-i

Cl

N CH 3 O

221.0

165.0

110.0

193.1

283.0

241.0


100

100

150

Nordiazepam-d5, methyl derivative

D

D

D

N D

D

300 287.0

V-3-B-ii N CH 3 O

112.5

82.1

250 261.0

Cl

C16H8D5ClN2O MW: 289.77

50

200

170.1

226.1 246.0

198.1

0 50

100

150

200

250

300


100

Nordiazepam, ethyl derivative C17H15ClN2O MW: 298.77

50

V-3-C-i

Cl

N

91.1

N C 2H 5 O

270.0

297.0

241.0

165.0

207.1


100

100

150

Nordiazepam-d5, ethyl derivative C17H10D5ClN2O MW: 303.80

50

200

D

D

N D

D

96.1

300

350

275.1

Cl D

250

301.1

V-3-C-ii N C 2H 5 O

246.1

170.1

212.1

0 50

100

150

200 m/z



250

300

350

281


Relative Int. (%)

100

50

Nordiazepam, propyl derivative

Cl

C18H17ClN2O MW: 312.79 91.1

N

311.1

269.0

284.1

V-3-D-i N C 3H 7 O

165.1

193.1

241.0

227.0


100

100

150

Nordiazepam-d5, propyl derivative C18H12D5ClN2O MW: 317.82 96.1

50

200

Cl D

D

D

N D

D

250

170.1

198.1

350 315.1

289.1

273.1

V-3-D-ii N C 3H 7 O

300

246.1

232.1

0 50

Relative Int. (%)

100

100

150

Nordiazepam, butyl derivative

250

V-3-E-i

350

165.1

325.1 298.1

N C 4H 9 N O

91.1

300

269.0

Cl

C19H19ClN2O MW: 326.82

50

200 m/z

241.0 193.1


100

100

150

Nordiazepam-d5, butyl derivative C19H14D5ClN2O MW: 331.85 96.1

50

200

D

D

N D

D

300

350 329.1

273.1

Cl D

250

V-3-E-ii

303.1

N C 4H 9 O

170.1

246.1 198.1

0 50

Relative Int. (%)

100

100

150

Nordiazepam, trimethylsilyl derivative

250

300

350

341.1

Cl

V-3-F-i

C18H19ClN2OSi MW: 342.89 73.1

50

200 m/z

N

N Si(CH3)3 O

327.0

91.1

227.0

269.0


100

100

150

Nordiazepam-d5, trimethylsilyl derivative C18H14D5ClN2OSi MW: 347.93 73.1 96.1

50

200

Cl D

D

D

N D

D

250

100

345.1

N Si(CH3)3 O

332.1 232.0

150

200 m/z



350

V-3-F-ii

0 50

300

250

273.0

300

350

282


Relative Int. (%)

100

327.1

Nordiazepam, t-butyldimethylsilyl derivative

50

Cl

C21H25ClN2OSi MW: 384.97

N

73.1

V-3-G-i N Si(CH3)2C(CH3)3 O

383.1


100

100

150

200

300

350

400

332.1

Nordiazepam-d5, t-butyldimethylsilyl derivative

50

250

Cl

C21H20D5ClN2OSi MW: 390.00

D

D

D

N D

D

V-3-G-ii N Si(CH3)2C(CH3)3 O

73.1

389.1

0 50

100

150

200

250 m/z



300

350

400

283

Figure V-4. Mass spectra of nitrazepam and its deuterated analogs (nitrazepam-d5): (A) methyl-derivatized; (B) ethyl-derivatized; (C) propyl-derivatized; (D) butyl-derivatized; (E) TMS-derivatized; (F) t-BDMS-derivatized.

Relative Int. (%)

100

O 2N

Nitrazepam (CAS NO.146-22-5), methyl derivative C16H13N3O3 MW: 295.29

50

57.1

N

N CH 3

294.0

248.1

221.0 207.0

O

165.1 192.0

110.1

85.1

267.1

V-4-A-i

281.0


100

100

150

Nitrazepam-d5 (CAS NO.136765-45-2), methyl derivative D C16H8D5N3O3 MW: 300.32 57.1 85.1

50

200 O 2N

D

111.1

300

N

N CH 3

207.0

O

350

272.1

V-4-A-ii

D

D D

250

298.1 252.1

225.1

300.1 284.0

170.0 197.0

0 50

Relative Int. (%)

100

100

150

Nitrazepam, ethyl derivative

N

91.1

250

300

281.1

234.1

N C 2H 5 O

207.1

165.1

57.1

350

308.1

V-4-B-i

O 2N

C17H15N3O3 MW: 309.32

50

200 m/z

262.1


100

100

150

Nitrazepam-d5, ethyl derivative

50

D

96.1

D

N

300

V-4-B-ii

D

D

250

350 312.1

O 2N D

C17H10D5N3O3 MW: 314.35

200

286.1

N C 2H 5

239.1

O

266.1

211.1

170.1

57.1

0 50

Relative Int. (%)

100

100

150

Nitrazepam, propyl derivative

O 2N

C18H17N3O3 MW: 323.35 91.1

50

200 m/z

N

250

300

350

322.1

V-4-C-i 280.1

N C 3H 7

295.1

234.1

O

206.1

165.1

276.1


100

100

150

Nitrazepam-d5, propyl derivative C18H12D5N3O3 MW: 328.38 96.1

50

200

O 2N D

D

D

N

300

284.1

N C 3H 7

350 326.1

V-4-C-ii

D

D

250

300.1

238.1

O

211.1

170.1

280.2

0 50

100

150

200 m/z



250

300

350

284

Figure V-4. (Continued) Relative Int. (%)

100

Nitrazepam, butyl derivative

V-4-D-i 50

91.1

336.1

O 2N

C19H19N3O3 MW: 337.37

N

280.1 234.1

N C 4H 9

309.1

O

205.1

165.1

252.1

57.1

0 50

100

Relative Int. (%)

100

V-4-D-ii 96.1

50

150

200

Nitrazepam-d5, butyl derivative C19H14D5N3O3 MW: 342.40

250

300

D

D

D

D N

N C 4H 9

314.2

238.1

O

257.1

211.1

170.1

57.1

340.2

284.1

O 2N D

350

0 50

100

Relative Int. (%)

100

V-4-E-i

150

200 m/z

Nitrazepam, trimethylsilyl derivative

N

73.1 91.1

300

350

352.1

O 2N

C18H19N3O3Si MW: 353.45

50

250

N Si(CH3)3

306.1

O

338.1

145.6

0 50

100

Relative Int. (%)

100

V-4-E-ii 50

150

C18H14D5N3O3Si MW: 358.48

73.1 96.1

250

300

100

O 2N D

D

D

D

D

150

350

N

400 356.2

N Si(CH3)3

310.1 343.1

O

147.6

0 50

200

Nitrazepam-d5, trimethylsilyl derivative

200

250

300

350

400


100

V-4-F-i 50

Nitrazepam, t-butyldimethylsilyl derivative C21H25N3O3Si MW: 395.53

73.1

338.1

O 2N

N

N Si(CH3)2C(CH3)3 O

292.1 394.2

145.7

0 50

100

Relative Int. (%)

100

V-4-F-ii

150

200

Nitrazepam-d5, t-butyldimethylsilyl derivative

300

D

D

D

D

D N

350

400

450

O

297.1 398.2

148.0

0 100

150

200

250 m/z



450

N Si(CH3)2C(CH3)3

73.1

50

400

343.2

O 2N

C21H20D5N3O3Si MW: 400.56

50

250

300

350

285

Figure V-5. Mass spectra of temazepam and its deuterated analogs (temazepam-d5): (A) underivatized; (B) methylderivatized; (C) ethyl-derivatized; (D) propyl-derivatized; (E) butyl-derivatized; (F) acetyl-derivatized; (G) TMSderivatized; (H) t-BDMS-derivatized. Relative Int. (%)

100

Temazepam (CAS NO.846-50-4) C16H13ClN2O2 MW: 300.74

50

77.1

228.0

Cl

300.0 257.0

195.0 N CH 3 N O 165.1 OH

91.1 105.0

V-5-A-i 271.0


100

100

150

50

Cl

D

96.1

300

227.1

195.0

350

262.1

D

D

82.1

250

305.1

Temazepam-d5 (CAS NO.136765-51-0) C16H8D5ClN2O2 MW: 305.77

200

110.1 D

D

N

O

V-5-A-ii 276.1

N CH 3

169.1

OH

0 50

100

Relative Int. (%)

100

150

250

300

50

N

77.1

127.0

350

271.0

Cl

V-5-B-i

57.1

200 m/z

N CH 3 O O CH 3

Temazepam, methyl derivative C17H15ClN2O2 MW: 314.77

255.0 314.1 207.0

165.0

0 50

100

150

Relative Int. (%)

100 D

300

D

N

D

127.0

82.1

350

276.1

Temazepam-d5, methyl derivative

D

D

57.1

250

Cl

V-5-B-ii 50

200

N CH 3 O O CH 3

C17H10D5ClN2O2 MW: 319.80

261.1

319.1 207.0

170.1

0 50

100

150

Relative Int. (%)

100

250

50

N

85.1

300

350

271.0

Cl

V-5-C-i 57.1

200 m/z

Temazepam, ethyl derivative C18H17ClN2O2 MW: 328.79

N CH 3

255.0

O O C 2H 5

328.1

207.0

0 50

100

Relative Int. (%)

100

150

85.1

300

350

276.1

D

D

D

N CH 3 N D O O C 2H 5

D

57.1

250

Cl

V-5-C-ii

50

200

400 Temazepam-d5, ethyl derivative

C18H12D5ClN2O2 MW: 333.82 260.1 333.1

207.0

0 50

100

150

200

250 m/z



300

350

400

286


Relative Int. (%)

100

271.0

Cl

Temazepam, propyl derivative

V-5-D-i 50

N

77.1

C19H19ClN2O2 MW: 342.82

N CH 3

255.0

O O C 3H 7

300.1

342.1

0 50

100

150

200

Relative Int. (%)

100

250

D

D

N

D

71.1

400

Temazepam-d5, propyl derivative

D

D

50

350

276.1

Cl

V-5-D-ii

300

C19H14D5ClN2O2 MW: 347.85

N CH 3

260.1

O O C 3H 7

305.1

347.2

0 50

100

150

200

250

300

350

400


100

97.1

57.1

50

271.0

Cl

V-5-E-i

N CH 3 N O O C 4H 9

111.1 125.1

Temazepam, butyl derivative C20H21ClN2O2 MW: 356.85

257.0 300.0

356.1

0 50

100

150

200

250

Relative Int. (%)

100

300

350

276.1

V-5-E-ii 50

Cl D

D

D

D

97.1

57.1

D

111.1 125.1

N

N CH 3 O O C 4H 9

400 Temazepam-d5, butyl derivative

C20H16D5ClN2O2 MW: 361.88

262.1 305.1

361.1

0 50

100

150

200

250

300

350

400


100

271.1

Cl

V-5-F-i 50

N

N CH 3 O O COCH 3

Temazepam, acetyl derivative C18H15ClN2O3 MW: 342.78

257.1

300.0

165.1

77.1

342.1


100

100

150

V-5-F-ii

200

D

300 276.1

Cl D

D

N

C18H10D5ClN2O3 MW: 347.81

N CH 3 O O COCH 3

262.1

305.1

170.1

82.1

350 Temazepam-d5, acetyl derivative

D

D

50

250

347.1

0 50

100

150

200 m/z



250

300

350

287


Relative Int. (%)

100

Temazepam, trimethylsilyl derivative

50

73.1

343.1

Cl

V-5-G-i

C19H21ClN2O2Si MW: 372.92

N CH 3 N O O Si(CH3)3

178.1

257.1 283.1

357.1

372.1

0 50

100

Relative Int. (%)

100

150

200

Temazepam-d5, trimethylsilyl derivative

73.1

300

D

D

D

D

D

180.1

N

350

400

348.1

Cl

C19H16D5ClN2O2Si MW: 377.95

50

250

V-5-G-ii N CH 3 O O Si(CH3)3

262.1 288.1

362.1

377.1

0 50

100

150

200

250

300

350

400


100

Temazepam, t-butyldimethylsilyl derivative

50

Cl

C22H27ClN2O2Si MW: 415.00 73.1

N

357.1

V-5-H-i 283.1

N CH 3

255.1

O

178.1 O Si(CH3)2C(CH3)3

102.1

385.2

399.1


100

100

150

Temazepam-d5, t-butyldimethylsilyl derivative

50

C22H22D5ClN2O2Si MW: 420.03 73.1

200

250

300

Cl D

D

D

D

D N

350

V-5-H-ii N CH 3 O O Si(CH3)2C(CH3)3

400

260.1 390.2

404.2

0 50

100

150

200

250 m/z

300



450

362.1

288.1

180.1

102.1

415.2

350

400

420.2

450

288

Figure V-6. Mass spectra of clonazepam and its deuterated analogs (clonazepam-d4): (A) methyl-derivatized; (B) ethyl-derivatized; (C) propyl-derivatized; (D) butyl-derivatized; (E) TMS-derivatized; (F) t-BDMS-derivatized.

Relative Int. (%)

100

O 2N

Clonazepam (CAS NO.1622-61-3), methyl derivative C16H12ClN3O3 MW: 329.74

50

75.0

Cl

N

N CH 3

328.0

302.0

266.0

O

191.0

165.1

127.1

294.1

248.1

V-6-A-i 220.0

313.1

0 50

100

Relative Int. (%)

100

150

200

Clonazepam-d4 (CAS NO.170082-15-2), methyl derivative D C16H8D4ClN3O3 D MW: 333.76

50

O 2N

129.0

78.1

N

Cl

300 298.1

V-6-A-ii

D

D

250

350

306.1

252.1

333.1 331.1

N CH 3

270.1

O

169.1

224.1

195.1

317.1

0 50

100

Relative Int. (%)

100

150

O 2N

Clonazepam, ethyl derivative C17H14ClN3O3 MW: 343.76 57.1 97.1

50

200 m/z

300

308.1

V-6-B-i N C 2H 5

N Cl

125.1

250

280.1

350

342.1 316.1

234.1 268.0

O

205.1

177.1

327.0

0 50

100

Relative Int. (%)

100

150

Clonazepam-d4, ethyl derivative C17H10D4ClN3O3 MW: 347.79

50 57.1

200 O 2N

D

D

D

N Cl

129.1

300

347.1

284.1

N C 2H 5

350 312.1

V-6-B-ii

D

97.1

250

320.1

238.1

O

266.1 181.1

209.1

331.1

0 50

Relative Int. (%)

100

100

150

O 2N

Clonazepam, propyl derivative C18H16ClN3O3 MW: 357.80

50

89.1

200 m/z

125.0

Cl

151.0

250

V-6-C-i

315.0 356.1 322.1

O

205.1

177.1

350

280.1

234.1

N C 3H 7

N

300

330.1

268.0


100

100

150

200

Clonazepam-d4, propyl derivative

50

V-6-C-ii

O 2N D

C18H12D4ClN3O3 MW: 361.82

250

D

D

155.1

97.5

Cl

284.1

238.1

D

129.1

300

N

O

209.1

400

319.1 326.1

N C 3H 7

181.1

350

361.1

334.1

271.0

0 50

100

150

200

250 m/z



300

350

400

289


Relative Int. (%)

100

Clonazepam, butyl derivative

315.0 336.1

234.1

C19H18ClN3O3 MW: 371.82

50

280.1

V-6-D-i

O 2N

125.0

N Cl

370.1

N C 4H 9 O

177.1

344.1

268.0

205.1


100

100

150

200

Clonazepam-d4, butyl derivative

D

D

D

N Cl

350

400

284.1 319.1

340.1

238.1

D

129.1

300

V-6-D-ii

O 2N

C19H14D4ClN3O3 MW: 375.84

50

250

N C 4H 9

373.1

O

209.1

181.1

348.1

271.1

0 50

100

150

200

250

300

350

400


100

73.1

Clonazepam, trimethylsilyl derivative

O 2N

387.1

352.1 306.1


50

V-6-E-i

N Cl

125.0

N Si(CH3)3

372.1

O

250.1

177.1

326.1

272.0


100

100 73.1

150

200

Clonazepam-d4, trimethylsilyl derivative

O 2N D


50

250

Cl

350 356.2

V-6-E-ii

D

400 391.1

310.1

D D

300

N

129.0

N Si(CH3)3

376.1

O

250.1

181.1

330.1

276.0

0 50

100

150

200

250

300

350

400


100

Clonazepam, t-butyldimethylsilyl derivative

O 2N


50

Cl

73.1

N

372.1

V-6-F-i N Si(CH3)2C(CH3)3 O

326.1

429.2


100

100

150

200

250

Clonazepam-d4, t-butyldimethylsilyl derivative

O 2N


50

300

D

D

D

Cl

D N

73.1

350

400

450

376.1

V-6-F-ii N Si(CH3)2C(CH3)3 O

330.1

433.2

0 50

100

150

200

250 m/z



300

350

400

450

290

Figure V-7. Mass spectra of 7-aminoclonazepam and its deuterated analogs (7-aminoclonazepam-d4): (A) [methyl]3derivatized; (B) [ethyl]2-derivatized; (C) [ethyl]3-derivatized; (D) propyl-derivatized; (E) [propyl]2-derivatized; (F) butyl-derivatized; (G) [butyl]2-derivatized; (H) PFP-derivatized; (I) HFB-derivatized; (J) [TMS]2-derivatized; (K) tBDMS-derivatized; (L) [t-BDMS]2-derivatized; (M) TFA/[TMS]2-derivatized; (N) [TFA]2/t-BDMS-derivatized; (O) TFA/[t-BDMS]2-derivatized; (P) PFP/TMS-derivatized; (Q) PFP/[TMS]2-derivatized; (R) PFP/[t-BDMS]2derivatized; (S) HFB/[t-BDMS]2-derivatized. Relative Int. (%)

100

7-Aminoclonazepam (CAS NO.4959-17-5), tri-methyl derivative

327.0 298.0

C18H18ClN3O MW: 327.81

50

V-7-A-i

N(CH3)2

N Cl

N–CH 3 O

131.6

284.0


100

100

150

200

300

350

400

331.0

7-Aminoclonazepam-d4, tri-methyl derivative

N(CH3)2 D

C18H14D4ClN3O MW: 331.83

50

250

302.0

D D

V-7-A-ii

D N Cl

N–CH 3 O

288.0

133.6

0 50

150

200

250

300

350

400

m/z


100 7-Aminoclonazepam, di-ethyl derivative C19H20ClN3O MW: 341.83

50

N Cl

341.0

V-7-B-i

NHC 2H 5

312.0

N–C 2 H 5

278.0

O

326.0

131.4


100

100

150

200

300

350

400

345.1

7-Aminoclonazepam-d4, di-ethyl derivative

NHC 2H 5

C19H16D4ClN3O MW: 345.86

50

250

D

D

D

N Cl

D

V-7-B-ii

N–C 2 H 5

317.0 282.1

O

133.4

330.0

0 50

150

200

250

300

350

m/z


100 7-Aminoclonazepam, tri-ethyl derivative

N(C2H5)2

C21H24ClN3O MW: 369.89

50

N Cl

400 354.0

V-7-C-i

369.1

N–C 2 H 5 O

267.9

296.0

326.0


100

100

150

200

7-Aminoclonazepam-d4, tri-ethyl derivative

N(C2H5)2 D

C21H20D4ClN3O MW: 373.91

50

250

D

D D

N Cl

300

350

400 358.1

V-7-C-ii

373.1

N–C 2 H 5 O

266.1

300.0

330.0

0 50


100

150

200


300

350

400

291


Relative Int. (%)

100

7-Aminoclonazepam, propyl derivative

NHC 3H 7

C18H18ClN3O MW: 327.81

50

NH N Cl

250.0

285.0

O

299.0

220.0

180.0

147.0

103.9

327.0

V-7-D-i


100

100

150

200

7-Aminoclonazepam-d4, propyl derivative

NHC 3H 7

C18H14D4ClN3O MW: 331.83

50

D

D

D

N Cl

D

300

350 331.0

V-7-D-ii

NH

147.0

105.0

250

254.0

O

289.0

303.0

224.0

184.0

0 50

Relative Int. (%)

100

100

150

200 m/z

7-Aminoclonazepam, di-propyl derivative

NHC 3H 7

300

350

369.1

V-7-E-i 340.0

C21H24ClN3O MW: 369.89

50

250

N Cl

N–C 3 H 7

298.0

O

255.0

203.0


100

100

150

200

7-Aminoclonazepam-d4, di-propyl derivative

NHC 3H 7 D

C21H20D4ClN3O MW: 373.91

50

250

350

400 373.1

V-7-E-ii

D

344.1

D

N Cl

D

300

N–C 3 H 7

302.0

O

259.0

203.0

0 50

100

150

200

250

300

350

400


100

7-Aminoclonazepam, butyl derivative C19H20ClN3O MW: 341.83

50

NH N Cl

147.0

341.0

V-7-F-i

NHC 4H 9

250.0

285.0

O

313.0

220.0

180.0


100

100

150

200

7-Aminoclonazepam-d4, butyl derivative

NHC 4H 9

C19H16D4ClN3O MW: 345.86

50

250

D

D

D

N Cl

D

147.0

350

254.0

400

345.1

V-7-F-ii

NH

184.0

300

289.0 317.0

O

224.0

0 50

100

150

200

250 m/z



300

350

400

292


Relative Int. (%)

100

7-Aminoclonazepam, di-butyl derivative C23H28ClN3O MW: 397.94

50

397.1

NHC 4H 9

V-7-G-i

N Cl

255.0

N–C 4 H 9

354.0

O

312.0

298.0


100

100

150

200

7-Aminoclonazepam-d4, di-butyl derivative

250

300

400

D

D

D

N Cl

D

N–C 4 H 9

358.1

O

316.1

302.0

259.0

450 401.1

NHC 4H 9

V-7-G-ii

C23H24D4ClN3O MW: 401.96

50

350

0 50

Relative Int. (%)

100

100

150

250 m/z

300

7-Aminoclonazepam, pentafluoropropionyl derivative

V-7-H-i

50

200

C18H11ClF5N3O2 MW: 431.74 167.1 193.0

119.0 69.0

350

50

100

150

Relative Int. (%)

119.0

50

220.1

200

256.0

282.0

250

C18H7D4ClF5N3O2 MW: 435.77 171.1 197.1

69.0

O

100

Relative Int. (%)

100

150

69.1

50

350

D

D

N Cl

224.1

169.0

100

Relative Int. (%)

100

150

260.0

O

286.0

250 m/z

100

150

V-7-I-i

400

450

452.0 481.0

446.0

NHCOC 3F7

207.0

220.1

N Cl

256.0

200

250

391.1

300

350

224.1

260.0

200

250

400

450 450.0

V-7-I-ii

NHCOC 3F7 D

D

D

N Cl

D

207.0

418.0

O

282.0

500 456.0

485.1

NH

286.0

300 m/z



372.1

350

422.1

O

395.0

0 50

435.0

345.0

300

69.0 C19H7D4ClF7N3O2 MW: 485.78 169.0 119.0

406.0

NH

7-Aminoclonazepam-d4, heptafluorobutyryl derivative

50

450

NH

0 50

400 400.0

NHCOC 2F5 D

C19H11ClF7N3O2 MW: 481.75 119.0

368.0

300

D

200

7-Aminoclonazepam, heptafluorobutyryl derivative

431.0

341.1

0 50

396.0

NH N Cl

7-Aminoclonazepam-d4, pentafluoropropionyl derivative

V-7-H-ii

450

402.0

NHCOC 2F5

0 100

400

350

400

450

500

293


Relative Int. (%)

100

NHSi(CH3)3

7-Aminoclonazepam, di-trimethylsilyl derivative

50

C21H28ClN3OSi2 MW: 430.09

73.1

429.2

394.2

V-7-J-i

N–Si(CH3)3

N Cl

414.1

O

314.1

219.1

0 50

100

Relative Int. (%)

100

150

200

250

7-Aminoclonazepam-d4, di-trimethylsilyl derivative

50

D

D

D

N Cl

D

350

400 398.2

V-7-J-ii

NHSi(CH3)3

C21H24D4ClN3OSi2 MW: 434.06

73.1

300

450 433.2

418.2

N–Si(CH3)3

318.1

O

219.1

0 50

100

Relative Int. (%)

100

150

200

250 m/z

7-Aminoclonazepam, t-butyldimethylsilyl derivative

50

300

350

400

450

342.1

NHSi(CH3)2C(CH3)3

V-7-K-i

NH

C21H26ClN3OSi MW: 399.99

N Cl

73.1

153.6

147.1

O

242.1

399.1

364.2

328.1

0 50

100

Relative Int. (%)

100

150

200

250

7-Aminoclonazepam-d4, t-butyldimethylsilyl derivative

50

D

D

D

N Cl

D

400

450

346.1

V-7-K-ii

NH O

246.1

155.6

147.1

350

NHSi(CH3)2C(CH3)3

C21H22D4ClN3OSi MW: 403.99 73.1

300

403.2

368.2

332.1

0 50

Relative Int. (%)

100

100

73.1

150

250 m/z

7-Aminoclonazepam, di-t-butyldimethylsilyl derivative C27H40ClN3OSi2 MW: 514.25

50

200

300

350

400

450

456.1

NHSi(CH3)2C(CH3)3

V-7-L-i N Cl

173.6 199.6

N–Si(CH3)2C(CH3)3

513.2

O

306.1

420.1

478.3


100

100 73.1

50

150

200

250

300

7-Aminoclonazepam-d4, di-t-butyldimethylsilyl derivative C27H36D4ClN3OSi2 MW: 518.27 175.3

350

400

450

D

D

N Cl

D

201.6

V-7-L-ii

N–Si(CH3)2C(CH3)3

517.2

O

310.1

424.2

0 50

100

150

200

250

300 m/z

350



550

460.2

NHSi(CH3)2C(CH3)3 D

500

400

450

482.3

500

550

294


Relative Int. (%)

100

73.0

7-Aminoclonazepam, trifluoroacetyl/di-trimethylsilyl derivative

N(Si(CH3)3)2

C23H27ClF3N3O2Si2 MW: 526.10

50

147.0

N Cl

V-7-M-i 525.1

490.1

N–COCF 3

510.1

O

221.0

410.0

348.1


100

100 73.0

150

200

250

7-Aminoclonazepam-d4, trifluoroacetyl/di-trimethylsilyl derivative

147.0

350

400

N(Si(CH3)3)2 D

D

D

N Cl

D

C23H23D4ClF3N3O2Si2 MW: 530.12

50

300

450

500 529.1

494.2

V-7-M-ii

550

N–COCF 3

514.1 414.1

O

352.1

221.0

0 50

Relative Int. (%)

100

100

73.1

200

250

300 m/z

350

400

450

N Cl

500

N–Si(CH3)2C(CH3)3

C25H24ClF6N3O3Si MW: 592.01

O

151.0

50 100

100 73.1

150

590.0

200

250

300

V-7-N-ii

350

400

450

500

D

D

D

N Cl

D

550

600

C25H20D4ClF6N3O3Si MW: 596.03

N–Si(CH3)2C(CH3)3 O

147.0

594.0

0

Relative Int. (%)

100

100

73.1

150

200

250

300

7-Aminoclonazepam, trifluoroacetyl/di-t-butyldimethylsilyl derivative

350 m/z

400

COCF 3 N(SiCH3)2C(CH3)3

C29H39ClF3N3O2Si2 MW: 610.26

50

650

7-Aminoclonazepam-d4, di-trifluoroacetyl/t-butyldimethylsilyl derivative

N(COCF3)2

50

50

550

7-Aminoclonazepam, di-trifluoroacetyl/t-butyldimethylsilyl derivative

N(COCF3)2

V-7-N-i

50

0

Relative Int. (%)

150

N Cl

450

500

V-7-O-i

550

600

650

552.1

N–SiCH3)2C(CH3)3 O

368.0

609.2

438.0


100

100 73.1

150

200

250

7-Aminoclonazepam-d4, trifluoroacetyl/di-t-butyldimethylsilyl derivative

350

400

COCF 3 N(SiCH3)2C(CH3)3


50

300

D

D

D

N Cl

D

149.0

450

500

550

600

650

556.1

V-7-O-ii

N–SiCH3)2C(CH3)3 O

372.0

613.2

442.0

0 50

100

150

200

250

300

350 m/z

400



450

500

550

600

650

295


Relative Int. (%)

100 73.0

50

468.1

7-Aminoclonazepam, pentafluoropropionyl/ trimethylsilyl derivative

NHSi(CH3)3

C21H19ClF5N3O2Si MW: 503.92 125.0

N Cl

V-7-P-i

503.1 488.0

N–COC 2 F 5

388.0

O

0 50

100

Relative Int. (%)

100 73.0

50

150

200

250

300

350

400

450

500

550

472.1

7-Aminoclonazepam-d4, pentafluoropropionyl/ trimethylsilyl derivative

V-7-P-ii

NHSi(CH3)3

C21H15D4ClF5N3O2Si MW: 507.95

D

D

D

N Cl

D

507.1 492.1

N–COC 2 F 5

392.0

O

129.0

0 50

100

Relative Int. (%)

100 73.0

150

200

250

7-Aminoclonazepam, pentafluoropropionyl/ di-trimethylsilyl derivative

350

N(Si(CH3)3)2

C24H27ClF5N3O2Si2 MW: 576.11

50

300 m/z

N Cl

400

450

500

550

540.2 575.2

V-7-Q-i

N–COC 2 F 5

560.1

460.1

O

348.1

125.0

420.1

0 50

100

Relative Int. (%)

100 73.0

150

200

250

7-Aminoclonazepam-d4, pentafluoropropionyl/ di-trimethylsilyl derivative C24H23D4ClF5N3O2Si2 MW: 580.13

50

300

350

D

D

N Cl

D

50

100

450

200

250

N–COC 2 F 5

350

600

579.2 564.2

464.1

O

300

550

V-7-Q-ii 424.1

352.1

150

500 544.2

N(Si(CH3)3)2 D

129.0

0

400

400

450

500

550

600


100

7-Aminoclonazepam, pentafluoropropionyl/ di-t-butyldimethylsilyl derivative

50

731.

COC 2 F 5 N(SiCH3)2C(CH3)3

C30H39ClF5N3O2Si2 MW: 660.27

N Cl

602.2

V-7-R-i


659.3

440.1

368.1

0 50

100

Relative Int. (%)

100

150

200

250

300

7-Aminoclonazepam-d4, pentafluoropropionyl/ di-t-butyldimethylsilyl derivative

50

73.1


350

400

COC 2 F 5 N(SiCH3)2C(CH3)3 D

D

D

N Cl

D

450

500

550

600

650

700

606.2

V-7-R-ii


663.3

444.1

372.1

0 50

100

150

200

250

300

350

400

450

m/z



500

550

600

650

700

296


Relative Int. (%)

100

73.1

50

7-Aminoclonazepam, heptafluorobutyryl/ di-t-butyldimethylsilyl derivative

N(Si(CH3)2C(CH3)3

652.1

C31H39ClF7N3O2Si2 MW: 710.27


N Cl

368.0

100

100 73.1

50

150

200

250

300

350

7-Aminoclonazepam-d4, heptafluorobutyryl/ di-t-butyldimethylsilyl derivative

200

250

D

D

D

N Cl

D

372.0

150

O

450

500

709.2

550

300

350

400 m/z

600

650

O

450

700

656.2

494.0

500

750

V-7-S-ii

N–Si(CH3)2C(CH3)3



490.0

N(Si(CH3)2C(CH3)3

0 100

400

N–Si(CH3)2C(CH3)3

COC 3 F 7


50

V-7-S-i

COC 3 F 7

713.3

550

600

650

700

750

297

Figure V-8. Mass spectra of prazepam and its deuterated analogs (prazepam-d5).

Relative Int. (%)

100 91.0

Cl

Prazepam (CAS NO.2955-38-6) C19H17ClN2O MW: 324.80

50

N

55.1 165.0

116.0

269.0

V-8-i N CH 2 O

295.0

241.0

324.0

205.0

0 50

100

Relative Int. (%)

100 96.1

150

200

Prazepam-d5 (CAS NO.152477-89-9) C19H12D5ClN2O MW: 329.83

50

D

Cl

D

V-8-ii

D

D

55.1

D

166.0

120.0

250

N

N CH 2 O

300 273.0

350

300.1 329.1

246.0

210.1

0 50

100

150

200 m/z



250

300

350

298

Figure V-9. Mass spectra of lorazepam and its deuterated analogs (lorazepam-d4): (A) [methyl]2-derivatized; (B) [ethyl]2-derivatized; (C) [propyl]2-derivatized; (D) [butyl]2-derivatized; (E) HFB-derivatized; (F) [TMS]2-derivatized; (G) [t-BDMS]2-derivatized. Relative Int. (%)

100

V-9-A-i

C17H14Cl2N2O2 MW: 349.21

50

305.0

Cl

Lorazepam (CAS NO.846-49-1), di-methyl derivative

N Cl

177.0

75.0

N CH 3

313.1

O O CH 3

289.0

255.0

348.0


100

100

150

200

300

350

C17H10D4Cl2N2O2 MW: 353.23

D

D

D

N Cl

D

181.1

75.0

400

309.0

Cl

Lorazepam-d4 (CAS NO.84344-15-0), di-methyl derivative

50

250

V-9-A-ii N CH 3

317.1

O O CH 3

293.0

259.0

352.1

0 50

100

150

200

250

300

350

400


100

319.0

Cl

Lorazepam, di-ethyl derivative

V-9-B-i 50

N Cl

102.1

N C 2H 5

C19H18Cl2N2O2 MW: 377.26

291.0

O O C 2H 5

177.1

138.0

275.0

305.1

341.1

376.1

0 50

100

150

Relative Int. (%)

100

200

250

300

350 323.1

Cl

V-9-B-ii

D

D

D

N Cl

D

50

N C 2H 5 O O C 2H 5

142.0

106.1

C19H14D4Cl2N2O2 MW: 381.29

295.0 181.1

279 .0

400

Lorazepam-d4, di-ethyl derivative

309.1

380.1

345.1

0 50

100

150

200

250

300

350

400


100

333.1

Cl

V-9-C-i 50

N Cl

N C 3H 7 O O C 3H 7

138.0

57.1

177.0

Lorazepam, di-propyl derivative C21H22Cl2N2O2 MW: 405.34

291.0

275.0

369.2

404.1

0 50

100

150

Relative Int. (%)

100

200

250

300

337.1

Cl

V-9-C-ii

D

D

D

N Cl

D

50

N C 3H 7 O O C 3H 7

142.0

57.1

350

181.1

400

450

Lorazepam-d4, di-propyl derivative C21H18D4Cl2N2O2 MW: 409.36

295.0 279.0

373.1

408.2

0 50

100

150

200

250 m/z



300

350

400

450

299


100

347.0

Cl

V-9-D-i 50

N Cl

57.1 138.1

C23H26Cl2N2O2 MW: 433.37

291.0

N C 4H 9 O O C 4H 9 207.0

275.0

Lorazepam, di-butyl derivative

333.1

432.1

397.2

0 50

100

150

200

Relative Int. (%)

100

250

300

350

Cl

V-9-D-ii

D

D

D

N Cl

D

50 57.1

142.1

400 351.1

O O C 4H 9

C23H22D4Cl2N2O2 MW: 437.39

295.0

N C 4H 9

279.0

207.1

337.1

401.1

0 50

100

150

200

Relative Int. (%)

100

300

350

69.0 119.0

N Cl

150.0

323.0

273.0

202.0

450

Lorazepam, heptafluorobutyryl derivative 442.0

N COC 3 F 7 O OH

436.3

400

407.0

Cl

V-9-E-i 50

250 m/z

450

Lorazepam-d4, di-butyl derivative

C19H9F7Cl2N2O3 MW: 517.18

423.0

387.0

0 50

100

150

200

250

Relative Int. (%)

100

300

350

400 411.1

Cl

V-9-E-ii

D

450

D

446.0 D

69.0

50

119.0

N COC 3 F 7 N D Cl O OH 207.0

150.0

550

Lorazepam-d4, heptafluorobutyryl derivative C19H5D4F7Cl2N2O3 MW: 521.20

327.0 390.0

277.0

500

427.0

0 50

100

Relative Int. (%)

100

150

200

250

300 m/z

73.1

400

450

500

V-9-F-i

Cl

C21H26Cl2N2O2Si2 MW: 465.52

N Si(CH3)3

N Cl

147.1

O

O Si(CH3)3

449.1

347.0

0 50

100

Relative Int. (%)

100

150

200

250

73.1

300

350

400

450

C21H22D4Cl2N2O2Si2 MW: 469.54

D

D

D

N Cl

D

N Si(CH3)3 O O Si(CH3)3

453.1

351.1

0 100

150

200

250

300 m/z



500

V-9-F-ii

Cl

147.1

50

464.2

433.2

Lorazepam-d4, di-trimethylsilyl derivative

50

550

429.2

Lorazepam, di-trimethylsilyl derivative

50

350

350

400

450

468.2

500

300


100

73.1

Lorazepam, di-t-butyldimethylsilyl 147.1 derivative

50

Cl

V-9-G-i

491.2

513.3

N Si(CH3)2C(CH3)3 N Cl O O Si(CH3)2C(CH3)3 347.0

C27H38Cl2N2O2Si2 MW: 549.68

533.2

549.2


100

100 73.1

150

200

250

300

Lorazepam-d4, di-t-butyldimethylsilyl 147.1 derivative

50

C27H34D4Cl2N2O2Si2 MW: 553.70

350 Cl D

D

D

N Cl

D

351.1

400

450

V-9-G-ii

500 495.2

550 517.3

N Si(CH3)2C(CH3)3 O O Si(CH3)2C(CH3)3

537.2

0 50

100

150

200

250

300

350 m/z



400

450

600

500

550

553.2

600

301

Figure V-10. Mass spectra of flunitrazepam and its deuterated analogs (flunitrazepam-d3, -d7).

Relative Int. (%)

100

Flunitrazepam (CAS NO.1622-62-4) O N 2 C16H12FN3O3 MW: 313.29

50 F

73.0

266.0 N CH 3

N

238.0

O

207.0

183.1

109.0

312.1

285.0

V-10-i

294.1

248.1

170.0


100

100

150 O 2N

Flunitrazepam-d3 C16H9D3FN3O3 MW: 316.31

50

N

CD 3

300

350 315.0

288.0 269.0

241.0

297.0

O

170.0

111.6

250

V-10-ii N

F

75.0

200

251.0

184.0


100

100

150

Flunitrazepam-d7

D

73.1

F

113.1

N

174.1

300

350 318.1

V-10-iii

D

D

250 292.1

O 2N D

C16H5D7FN3O3 MW: 320.23

50

200

N CD 3 O

245.1 188.1

272.1

301.1

255.1

207.0

0 50

100

150

200 m/z



250

300

350

302

Figure V-11. Mass spectra of 7-aminoflunitrazepam and its deuterated analogs (7-aminoflunitrazepam-d3, -d7): (A) underivatized; (B) [methyl]2-derivatized; (C) ethyl-derivatized; (D) [ethyl]2-derivatized; (E) propyl-derivatized; (F) butyl-derivatized; (G) acetyl-derivatized; (H) TFA-derivatized; (I) PFP-derivatized; (J) HFB-derivatized; (K) TMSderivatized; (L) TFA/TMS-derivatized; (M) TFA/t-BDMS-derivatized; (N) PFP/TMS-derivatized; (O) PFP/t-BDMSderivatized; (P) HFB/TMS-derivatized; (Q) HFB/t-BDMS-derivatized. Relative Int. (%)

100

7-Aminoflunitrazepam (CAS NO.34084-50-9) C16H14FN3O MW: 283.30

50

283.1

H 2N

255.0

V-11-A-i

N

F

N CH 3 O

264.1


100

100

150

200

7-Aminoflunitrazepam-d3

250

300 286.1

H 2N

C16H11D3FN3O MW: 286.32

V-11-A-ii

50

258.1 N CD 3 N O F

267.1


100

100

150

200

7-Aminoflunitrazepam-d7

50

300 290.1

H 2N

V-11-A-iii

C16H7D7FN3O MW: 290.34

250

D

D

D

F

D N

262.1 N CD 3 O

271.1

0 50

100

150

200

250

300


100

7-Aminoflunitrazepam, di-methyl derivative C18H18FN3O MW: 311.35

50

311.1

N(CH3)2

V-11-B-i

N

F

282.1

N CH 3 O

266.0

127.0


100

100

150

7-Aminoflunitrazepam-d3, di-methyl derivative C18H15D3FN3O MW: 314.37

50

200

250

300

N(CH3)2

V-11-B-ii

N

F

350 314.1

285.1

N CD 3 O

269.1

128.5


100

100 7-Aminoflunitrazepam-d7, di-methyl derivative

150

250

300

D

350 318.1

N(CH3)2

V-11-B-iii

C18H11D7FN3O MW: 318.40

50

200

D

289.1

D D

F

N

N CD 3 O

273.1

130.5

0 50

100

150

200 m/z



250

300

350

303


Relative Int. (%)

100

7-Aminoflunitrazepam, ethtyl derivative C18H18FN3O MW: 311.36

50

311.1

V-11-C-i

NHC 2H 5

282.1 N CH 3 N F O

57.1

296.1

268.1

207.0

149.0

0 50

100

Relative Int. (%)

100

150

200

7-Aminoflunitrazepam-d3, ethtyl derivative

N

F

300

285.1

N CD 3 O

149.0

350 314.1

V-11-C-ii

NHC 2H 5

C18H15D3FN3O MW: 314.37

50

250

299.0

271.0

212.0

0 50

100

Relative Int. (%)

100

150

7-Aminoflunitrazepam-d7, ethtyl derivative C18H11D7FN3O MW: 318.40

50

200

250

300 318.2

V-11-C-iii

NHC 2H 5 D

D

D

N CD 3 N O F

350

289.2 D

57.1

303.2

207.0

150.4

275.2

0 50

Relative Int. (%)

100

100

150

7-Aminoflunitrazepam, di-ethyl derivative

250

300

350 324.1

N(C2H5)2

C20H22FN3O MW: 339.41

50

200 m/z

V-11-D-i

N CH 3 N F O

339.1

266.1

311.1


100

100

150

200

7-Aminoflunitrazepam-d3, di-ethyl derivative

50

N

F

300

350 327.1

N(C2H5)2

C20H19D3FN3O MW: 342.43

250

V-11-D-ii

342.1

N CD 3

O

269.0

313.1


100

100

150

7-Aminoflunitrazepam-d7, di-ethyl derivative C20H15D7FN3O MW: 346.45

50

200

300

350 331.2

N(C2H5)2

V-11-D-iii

D

D

D

N CD 3 N O F

D

250

346.2

273.1

318.2

0 50

100

150

200 m/z



250

300

350

304


Relative Int. (%)

100

7-Aminoflunitrazepam, propyl derivative C19H20FN3O MW: 325.38

50

N

F

57.1

296.1

NHC 3H 7

V-11-E-i

325.1

N CH 3 O

268.1

207.0

147.5

0 50

100

Relative Int. (%)

100

150

200

7-Aminoflunitrazepam-d3, propyl derivative

N

F

300

350

299.1

NHC 3H 7

C19H17D3FN3O MW: 328.40

50

250

328.1

V-11-E-ii

N CD 3 O

271.0

149.0

0 50

100

Relative Int. (%)

100

150

200

7-Aminoflunitrazepam-d7, propyl derivative

NHC 3H 7 D

C19H13D7FN3O MW: 332.43

50 57.1

250

D

N

F

350 303.2

V-11-E-iii

D

D

300

332.2

N CD 3 O

275.1

207.0

150.6

0 50

Relative Int. (%)

100

100

150

200 m/z

7-Aminoflunitrazepam, butyl derivative

N

F

300

339.2

V-11-F-i

N CH 3 O

310.2 268.1

207.0

147.5

350

296.1

NHC 4H 9

C20H22FN3O MW: 339.41

50

250

320.2


100

100

150

200

7-Aminoflunitrazepam-d3, butyl derivative

N

F

300

350

299.1

NHC 4H 9

C20H19D3FN3O MW: 342.42

50

250

342.1

V-11-F-ii

N CD 3 O

313.1 271.0

149.0

323.1


100

100

150

200

7-Aminoflunitrazepam-d7, butyl derivative

D

D

D

F

D

149.0

N

300

350 303.1

NHC 4H 9

C20H15D7FN3O MW: 346.45

50

250

346.2

V-11-F-iii

N CD 3 O

317.2 275.2

207.0

327.2

0 50

100

150

200 m/z



250

300

350

305


Relative Int. (%)

100

7-Aminoflunitrazepam, acetyl derivative C18H16FN3O2 MW: 325.34

50

325.1

NHCOCH3

V-11-G-i

N CH 3 N F O

255.0

297.0

306.1


100

100

150

200

7-Aminoflunitrazepam-d3, acetyl derivative

NHCOCH3

C18H13D3FN3O2 MW: 328.36

50

250

300

V-11-G-ii

N CD 3 N F O

350 328.1

300.1 309.1

258.0


100

100

150

200

7-Aminoflunitrazepam-d7, acetyl derivative

D

D

D

F

D N

300

350 332.1

NHCOCH3

C18H9D7FN3O2 MW: 332.38

50

250

V-11-G-iii

N CD 3 O

304.1 313.1

262.1

0 50

Relative Int. (%)

100

100

150

200 m/z

7-Aminoflunitrazepam, trifluoroacetyl derivative

F

N

300

350

351.1

NHCOCF3

C18H13F4N3O2 MW: 379.31

50

250

V-11-H-i

N CH 3 O

379.1

360.1 280.1

69.1


100

100

150

200

7-Aminoflunitrazepam-d3, trifluoroacetyl derivative

250

50

F

N

350

400 354.0

NHCOCF3

C18H10D3F4N3O2 MW: 382.33

300

382.1

V-11-H-ii

N CD 3 O

363.1 283.0

69.0


100

100

150

200

7-Aminoflunitrazepam-d7, trifluoroacetyl derivative

NHCOCF3

C18H6D7F4N3O2 MW: 386.35

50

250

D

D

D

F

D N

300

350

400 358.1

V-11-H-iii

386.1

N CD 3

367.1

O

287.1

69.1

0 50

100

150

200

250 m/z



300

350

400

306


Relative Int. (%)

100

7-Aminoflunitrazepam, pentafluoropropionyl derivative C19H13F6N3O2 MW: 429.32

50

400.1

NHCOC 2F5

N

F

429.1

V-11-I-i

N CH 3 O

119.0

410.1

226.1

254.1


100

100

150

200

7-Aminoflunitrazepam-d3, pentafluoropropionyl derivative

300

N

F

350

400

450 432.1

404.0

V-11-I-ii

NHCOC 2F5

C19H10D3F6N3O2 MW: 432.33

50

250

N CD 3

413.1

O

119.0

229.0

257.0


100

100

150

200

7-Aminoflunitrazepam-d7, pentafluoropropionyl derivative C19H6D7F6N3O2 MW: 436.36

50

250

300

D

F

N

450

V-11-I-iii

D

D

400 408.1

NHCOC 2F5 D

350

436.2 417.1

N CD 3 O

233.1

119.0

261.1

0 50

Relative Int. (%)

100

100

150

7-Aminoflunitrazepam, heptafluorobutyryl derivative

50

200

250 m/z

300

350

400

451.1

C20H13F8N3O2 MW: 479.32

N

F

226.1

69.1

479.1

NHCOC 3F7

V-11-J-i

450

460.1

N CH 3 O

254.1


100

100

150

7-Aminoflunitrazepam-d3, heptafluorobutyryl derivative

200

250

300

350

N

F

229.0

69.0

450 454.1

NHCOC 3F7

V-11-J-ii

C20H10D3F8N3O2 MW: 482.34

50

400

500 482.1

463.1

N CD 3 O

257.0


100

100

150

7-Aminoflunitrazepam-d7, heptafluorobutyryl derivative C20H6D7F8N3O2 MW: 486.37 69.0 131.0

50

200

250

300

350

D

233.1

F

N

500 486.1

D

D D

450 458.1

NHCOC 3F7

V-11-J-iii

150.0

400

467.1

N CD 3 O

261.1

0 50

100

150

200

250

300 m/z



350

400

450

500

307


Relative Int. (%)

100

7-Aminoflunitrazepam, trimethylsilyl derivative

V-11-K-i

C19H22FN3OSi MW: 355.48

50

355.2

NHSi(CH3)3

F

73.1

N

N CH 3 O

327.1 336.1

254.1


100

100

150

200

7-Aminoflunitrazepam-d3, trimethylsilyl derivative

250

350

400 358.1

NHSi(CH3)3

V-11-K-ii

330.1

C19H19D3FN3OSi MW: 358.50

50

300

N CD 3 N O F

73.1

339.1

257.1


100

100

150

200

7-Aminoflunitrazepam-d7, trimethylsilyl derivative

250

50

350

D

400 362.2

NHSi(CH3)3

V-11-K-iii

C19H15D7FN3OSi MW: 362.52

300

D

334.2 D D

73.1

F

N

N CD 3 O

343.1

261.1

0 50

100

150

200

250

300

350

400


100

451.2

7-Aminoflunitrazepam, trifluoroacetyl/trimethylsilyl derivative

Si(CH3)3

V-11-L-i

NCOCF3

C21H21F4N3O2Si MW: 451.49

50

280.0

73.0

F

N

423.1

432.1

N CH 3 O


100

100

150

200

7-Aminoflunitrazepam-d3, trifluoroacetyl/trimethylsilyl derivative

250

350

400

Si(CH3)3

V-11-L-ii

C21H18D3F4N3O2Si MW: 454.51

50

300

450

500 454.2

426.1

NCOCF3

283.1

73.0

F

N

435.2

N CD 3 O


100

100

150

200

7-Aminoflunitrazepam-d7, trifluoroacetyl/trimethylsilyl derivative

50

250

300

350 Si(CH3)3

V-11-L-iii 287.1

450

500 458.2

430.2

NCOCF3 D

C21H14D7F4N3O2Si MW: 458.53

400

D

D

73.0

D

F

N

439.1

N CD 3 O

0 50

100

150

200

250

300 m/z



350

400

450

500

308


Relative Int. (%)

100 73.1

50

7-Aminoflunitrazepam, trifluoroacetyl/t-butyldimethylsilyl derivative C24H27F4N3O2Si MW: 493.57

436.1

Si(CH3)2C(CH3) 3

V-11-M-i

NCOCF3

287.1

196.1

280.1

219.1

F

N

N CH 3 O

493.2 386.1

0 50

100

Relative Int. (%)

100

150

200

250

7-Aminoflunitrazepam-d3, trifluoroacetyl/t-butyldimethylsilyl derivative

50 73.0

300

350

199.0

222.0

283.0

450

500

439.1

Si(CH3)2C(CH3) 3

V-11-M-ii

C24H24D3F4N3O2Si MW: 496.59

400

NCOCF3

496.2

290.0 F

N

N CD 3 O

389.1

0 50

100

Relative Int. (%)

100

150

200

250

7-Aminoflunitrazepam-d7, trifluoroacetyl/t-butyldimethylsilyl derivative

50

73.1

300

350

287.1

500

443.2

NCOCF3

290.1

199.1

450

Si(CH3)2C(CH3) 3

V-11-M-iii

C24H20D7F4N3O2Si MW: 500.61 149.0

400

D

D

D

F

D

222.1

N

N CD 3 O

393.1 498.2

0 50

100

150

200

250

300

350

400

450

500


100

7-Aminoflunitrazepam, pentafluoropropionyl/ trimethylsilyl derivative

50

Si(CH3)3

C22H21F6N3O2Si MW: 501.50 73.0

N

F

N CH 3 280.1 O

501.2

473.1

V-11-N-i

NCOC 2F 5

482.1 352.1

0 50

100

Relative Int. (%)

100

150

200

250

7-Aminoflunitrazepam-d3, pentafluoropropionyl/ trimethylsilyl derivative

Si(CH3)3

73.0

N

F

N CD 3 O

350

400

450

500

550 504.2

476.2

V-11-N-ii

NCOC 2F 5

C22H18D3F6N3O2Si MW: 504.52

50

300

485.2 355.1

283.1

0 50

100

Relative Int. (%)

100

150

200

250

7-Aminoflunitrazepam-d7, pentafluoropropionyl/ trimethylsilyl derivative C22H14D7F6N3O2Si MW: 508.54

400

450

500

550 508.2

V-11-N-iii

NCOC 2F 5 D

D D

73.0

350

480.2

Si(CH3)3 D

50

300

F

N

N CD 3 O

489.2 359.1

287.1

0 50

100

150

200

250

300 m/z

350



400

450

500

550

309


Relative Int. (%)

100

50

73.1

7-Aminoflunitrazepam, pentafluoropropionyl/t-butyl dimethylsilyl derivative

V-11-O-i

C25H27F6N3O2Si MW: 543.58

246.1

Si(CH3)2C(CH3) 3

486.1

NCOC 2F 5

337.1 280.1

N CH 3 O

N

F

543.2

0 50

100

150

200

250

300

350

400

Relative Int. (%)

100 7-Aminoflunitrazepam-d3, pentafluoropropionyl/t-butyl dimethylsilyl derivative

50

73.0

C25H24D3F6N3O2Si MW: 546.59

450

Si(CH3)2C(CH3) 3

V-11-O-ii 249.0

500

550

600

550

600

489.1

NCOC 2F 5

340.0 283.0

F

546.2

N CD 3 O

N

0 50

100

Relative Int. (%)

100

150

200

7-Aminoflunitrazepam-d7, pentafluoropropionyl/t-butyl dimethylsilyl derivative

50

73.1

250

300

350

400

Si(CH3)2C(CH3) 3

V-11-O-iii

500 493.2

NCOC 2F 5 D

C25H20D7F6N3O2Si MW: 550.62

450

D

340.1

249.1

D

287.1

D

F

550.3

N CD 3 O

N

0 50

100

150

200

250

300

350

400

450

500

550

600


100

7-Aminoflunitrazepam, heptafluorobutyryl/ trimethylsilyl derivative

50 73.0

551.2

Si(CH3)3

V-11-P-i

523.1

NCOC 3F 7

C23H21F8N3O2Si MW: 551.50 280.1

N

F

532.2

N CH 3 O

402.1

0 50

100

Relative Int. (%)

100

150

200

7-Aminoflunitrazepam-d3, heptafluorobutyryl/ trimethylsilyl derivative

50 73.1

250

300

350

400

450

500

550 554.2

Si(CH3)3

V-11-P-ii

526.1

NCOC 3F 7

C23H18D3F8N3O2Si MW: 554.52 283.1

N

F

600

535.2

N CD 3

405.1

O

0 50

100

Relative Int. (%)

100

150

200

7-Aminoflunitrazepam-d7, heptafluorobutyryl/ trimethylsilyl derivative

50 73.0

C23H14D7F8N3O2Si MW: 558.55

250

300

350

400

450

500

550

600 558.2

Si(CH3)3

V-11-P-iii

530.2

NCOC 3F 7

287.1

D

D

D

N CD 3 N F O

D

539.2 409.1

0 50

100

150

200

250

300

350 m/z



400

450

500

550

600

310


Relative Int. (%)

100

7-Aminoflunitrazepam, heptafluorobutyryl/t-butyldimethylsilyl derivative 73.1

50

Si(CH3)2C(CH3) 3

V-11-Q-i

NCOC 3F 7

296.1

C26H27F8N3O2Si MW: 593.58

387.1

280.1

536.1

N

F

N CH 3 O

593.2

0 50

100

Relative Int. (%)

100

150

200

250

300

7-Aminoflunitrazepam-d3, heptafluorobutyryl/t-butyldimethylsilyl derivative

50

73.0

350

400

450

500

Si(CH3)2C(CH3) 3

V-11-Q-ii

550

600

650

600

650

539.1

NCOC 3F 7

299.0

C26H24D3F8N3O2Si MW: 596.60

390.0

283.0

N

F

596.2

N CD 3 O

0 50

100

Relative Int. (%)

100

150

200

250

7-Aminoflunitrazepam-d7, heptafluorobutyryl/t-butyldimethylsilyl derivative 73.1

50

300

350

400

450

V-11-Q-iii 299.1

C26H20D7F8N3O2Si MW: 600.63

390.1

287.1

500

Si(CH3)2C(CH3) 3

550 543.2

NCOC 3F 7

D

D

D

F

D N

600.3

N CD 3 O

0 50

100

150

200

250

300

350 m/z

400



450

500

550

600

650

311

Figure V-12. Mass spectra of N-desalkylflurazepam and its deuterated analogs (N-desalkylflurazepam-d4): (A) underivatized; (B) methyl-derivatized; (C) [methyl]2-derivatized; (D) ethyl-derivatized; (E) propyl-derivatized; (F) butyl-derivatized; (G) acetyl-derivatized; (H) TMS-derivatized; (I) t-BDMS-derivatized. Relative Int. (%)

100

N-Desalkylflurazepam (CAS NO.2866-65-9), C15H10ClFN2O MW: 288.70

50

259.0

Cl

V-12-A-i

288.0

NH F

73.0

111.9

N

O

269.0 207.0

177.1

138.0

231.9


100

100

150

200

N-Desalkylflurazepam-d4 D

D

D

F

V-12-A-ii

D

73.0

292.0

NH

N

O

138.0

114.0

300

263.0

Cl

C15H6D4ClFN2O MW: 292.73

50

250

273.0 207.0

181.0

235.0

0 50

100

150

200

250

300


100

N-Desalkylflurazepam, methyl derivative

Cl

C16H12ClFN2O MW: 302.73

50

F

N

V-12-B-i N CH 3

301.0

283.0

O

183.0

109.1

274.0

211.0

239.0


100

100

150

N-Desalkylflurazepam-d4, methyl derivative

50

300

350 306.0

278.0

D

D D

250

V-12-B-ii

Cl

D


200

F

N

110.1

287.0

N CH 3 O

187.0

215.0

243.0

0 50

Relative Int. (%)

100

100

150

N-Desalkylflurazepam, di-methyl derivative

200 m/z Cl

C17H14ClFN2O MW: 316.75

50

F

N

250

V-12-C-i

350

275.0

N CH 3

315.0 297.0

OCH3

183.0

102.0

300

211.0

239.0


100

100

150

N-Desalkylflurazepam-d4, di-methyl derivative C17H10D4ClFN2O MW: 320.78

50

200 Cl

D

D

D

F

D

106.0

N

250

V-12-C-ii N CH 3

300

350

279.0

301.0 318.0

OCH3

187.0

215.0

243.0

0 50

100

150

200 m/z



250

300

350

312


Relative Int. (%)

100

N-Desalkylflurazepam, ethyl derivative C17H14ClFN2O MW: 316.76

50

288.0

Cl

F

109.0

N

V-12-D-i N C 2H 5

297.0 259.0

O

183.0

162.9

315.0

245.0


100

100

150

N-Desalkylflurazepam-d4, ethyl derivative

D

113.0

F

N

300

350

V-12-D-ii

D

D

250

292.0

Cl D


50

200

320.1 301.0

N C 2H 5

263.0

O

187.0

166.0

249.0

0 50

Relative Int. (%)

100

100

150

N-Desalkylflurazepam, propyl derivative

200 m/z Cl

C18H16ClFN2O MW: 330.78

50

N

F

109.0

250

V-12-E-i N C 3H 7 O

300

288.0

166.0

329.0

302.0 311.0

269.0

183.0

350

259.0 211.0


100

100

150

N-Desalkylflurazepam-d4, propyl derivative

D

F

113.0

N

300

V-12-E-ii

D

D

250

350

292.0

Cl

D


50

200

O

166.0

315.1

273.0

N C 3H 7

332.1

306.0

263.0 187.0

215.0

0 50

Relative Int. (%)

100

100

150

N-Desalkylflurazepam, butyl derivative 109.0 C19H18ClFN2O MW: 344.81

50

200 m/z

Cl

N

F

250

300

287.0

V-12-F-i N C 4H 9

183.0

259.0

211.0

O

350

343.0 269.0

316.0

325.1

245.0

75.0


100

100

150

N-Desalkylflurazepam-d4, butyl derivative C19H14D4ClFN2O MW: 348.83

50

200

Cl

113.1

D

D

D

F

D N

250

V-12-F-ii N C 4H 9

187.1

263.0

215.1

O

300

350

292.0 346.1

273.0 320.1

329.1

249.0

75.0

0 50

100

150

200 m/z



250

300

350

313


Relative Int. (%)

100

N-Desalkylflurazepam, acetyl derivative

V-12-G-i

259.0

C17H12ClFN2O2 MW: 330.74 109.0

50

288.0

Cl

N

F

165.9

N COCH 3

269.0 302.0

O

75.0

330.0

0 50

100

Relative Int. (%)

100

150

200 Cl

C17H8D4ClFN2O2 MW: 334.76

D

D

350

D

F

V-12-G-ii 263.0

D

165.9

113.0

300 292.0

N-Desalkylflurazepam-d4, acetyl derivative

50

250

273.0

N COCH 3

N

306.0

O

71.1

334.0

0 50

100

Relative Int. (%)

100

150

200 m/z

N-Desalkylflurazepam, trimethylsilyl derivative

50

73.1

250

Cl

300

350

359.1

V-12-H-i 341.1

C18H18ClFN2OSi MW: 360.89

N

F

N Si(CH3)3 O

245.0

166.0

109.1

0 50

100

Relative Int. (%)

100

150

200

N-Desalkylflurazepam-d4, trimethylsilyl derivative 73.1

50

250

D

N

F

400 364.1

V-12-H-ii

D

D

350 345.1

Cl D

C18H14D4ClFN2OSi MW: 364.91

N Si(CH3)3 O

166.0

113.1

300

249.1

0 50

100

150

200

250

300

350

400


100

N-Desalkylflurazepam, t-butyldimethylsilyl derivative

50

C21H24ClFN2OSi MW: 402.96

N

F

73.1

345.1

Cl

V-12-I-i N Si(CH3)2C(CH3)3 O

192.1

402.1


100

100

150

200

250

400

450

V-12-I-ii

Cl D

D

D

F

D

C21H20D4ClFN2OSi MW: 406.99 73.1

350 349.1

N-Desalkylflurazepam-d4, t-butyldimethylsilyl derivative

50

300

N

N Si(CH3)2C(CH3)3 O

196.1

406.2

0 50

100

150

200

250 m/z



300

350

400

450

314

Figure V-13. Mass spectra of N-desmethylflunitrazepam and its deuterated analogs (N-desmethylflunitrazepam-d4): (A) [methyl]2-derivatized; (B) ethyl-derivatized; (C) propyl-derivatized; (D) butyl-derivatized; (E) acetyl-derivatized; (F) TMS-derivatized; (G) t-BDMS-derivatized. Relative Int. (%)

100

N-Desmethylflunitrazepam (CAS NO.2558-30-7), di-methyl derivative

50

V-13-A-i

O 2N

C17H14FN3O3 MW: 327.31

N CH 3

N

F

286.0

238.1

OCH3

326.1

308.1

183.1


100

100

150

200

N-Desmethylflunitrazepam-d4, di-methyl derivative D

300

350

290.1

V-13-A-ii

O 2N

C17H10D4FN3O3 MW: 331.33

50

250

D

D D

N CH 3 OCH3

N

F

312.1

242.1

329.1

187.1

0 50

Relative Int. (%)

100

100

150

200 m/z

N-Desmethylflunitrazepam, ethyl derivative

350

V-13-B-i 300.1

N C 2H 5 O

N

F

109.1

300

326.1

O 2N

C17H14FN3O3 MW: 327.31

50

250

252.1 224.1

183.1

308.1 280.1


100

100

150

200

300

350 329.1

N-Desmethylflunitrazepam-d4, ethyl derivative

O 2N

C17H10D4FN3O3 MW: 331.33

50

250

D

D

D

F

D

113.1

N

V-13-B-ii N C 2H 5 O

256.1

228.1

187.1

304.1 312.1 283.1

0 50

Relative Int. (%)

100

100

150

200 m/z

N-Desmethylflunitrazepam, propyl derivative

O 2N

C18H16FN3O3 MW: 341.34

50

109.1

300

350

299.0

V-13-C-i

N C 3H 7 N F O

183.1

250

340.1

313.1 322.1

252.1 280.1

224.1


100

100

150

200

N-Desmethylflunitrazepam-d4, propyl derivative C18H12D4FN3O3 MW: 345.36

50

O 2N D

113.1

D

F

N

300

O

187.1

343.1

317.1 326.1

284.1

N C 3H 7

350 303.1

V-13-C-ii

D

D

250

255.1

227.1

0 50

100

150

200 m/z



250

300

350

315


Relative Int. (%)

100

N-Desmethylflunitrazepam, butyl derivative C19H18FN3O3 MW: 355.36

50

O 2N

109.1

N

F

298.1

V-13-D-i 252.1

N C 4H 9 O 183.1

224.1

280.1

354.1

327.1

57.1


100

100

150

N-Desmethylflunitrazepam-d4, butyl derivative C19H14D4FN3O3 MW: 359.39

50

200

D

D

D

F

300

350

400 357.1

301.1

V-13-D-ii

O 2N

284.1

D

113.1

250

N

N C 4H 9 O

57.1

228.1

187.1

331.1

255.1

0 50

100

150

200

250

300

350

400


100

260.0

O 2N

50

123.0 75.0

57.0

F

95.0

N

N-Desmethylflunitrazepam, acetyl derivative

V-13-E-i

C17H12FN3O4 MW: 341.29

N COCH 3 O

179.0

165.0

213.0

302.0

241.0

0 50

100

150

200

250

300

Relative Int. (%)

100 O 2N D

50 99.0

127.0

D D

57.1 71.1

V-13-E-ii

D

350

N-Desmethylflunitrazepam-d4, 264.0 acetyl derivative C17H8D4FN3O4 MW: 345.32

N COCH 3 N F O 179.0

165.0

245.0

217.0

306.0

0 50

100

Relative Int. (%)

100 73.1

150

200 m/z

300

350

371.1

N-Desmethylflunitrazepam, trimethylsilyl derivative

O 2N

C18H18FN3O3Si MW: 371.44

50

250

V-13-F-i 352.1

N Si(CH3)3 N F O

109.1

250.1

154.6

356.1

324.1 306.1


100

100 73.1

150

200

N-Desmethylflunitrazepam-d4, trimethylsilyl derivative C18H14D4FN3O3Si MW: 375.46

50

250 O 2N

D

V-13-F-ii

D

D D

113.1

F

300

N

N Si(CH3)3 O

250.1

156.5

350

400 375.1

356.1 360.1

310.1

327.1

0 50

100

150

200

250 m/z



300

350

400

316


Relative Int. (%)

100

356.1

N-Desmethylflunitrazepam, t-butyldimethylsilyl derivative

50

C21H24FN3O3Si MW: 413.52 73.1

V-13-G-i

O 2N

F

N

N Si(CH3)2C(CH3)3 O

310.1

154.6

398.1


100

100

150

200

350

400

D

D

D

F

D N

N Si(CH3)2C(CH3)3 O

314.1

156.5

402.2

0 50

100

150

200

250 m/z



450

V-13-G-ii

O 2N

C21H20D4FN3O3Si MW: 417.54 73.1

300

360.1

N-Desmethylflunitrazepam-d4, t-butyldimethylsilyl derivative

50

250

413.2

300

350

400

417.2

450

317

Figure V-14. Mass spectra of 2-hydroxyethylflurazepam and its deuterated analogs (2-hydroxyethylflurazepam-d4): (A) underivatized; (B) butyl-derivatized; (C) TMS-derivatized; (D) t-BDMS-derivatized. Relative Int. (%)

100

2-Hydroxyethylflurazepam (CAS NO.29071-53-3) C17H14ClFN2O2 MW: 332.76

50

288.0

Cl

V-14-A-i

N CH2CH2OH N F O 183.0

109.0

75.0

211.0

273.0 331.0

304.0

245.0

152.0


100

100

150

2-Hydroxyethylflurazepam-d4 D

D

F

113.0

N

300

350

292.0

V-14-A-ii

D

D

75.0

250

Cl

C17H10D4ClFN2O2 MW: 336.78

50

200

N CH2CH2OH O

308.0

249.0

215.0

187.0

277.0 334.1

152.0

0 50

100

150

200 m/z

250

Relative Int. (%)

100

288.0

Cl

50

N

F

57.1

300

2-Hydroxyethylflurazepam, butyl derivative

V-14-B-i N CH 2—CH 2O—C 4H 9 O

207.0

183.1

117.1

350

C21H22ClFN2O2 MW: 388.86

273.1 260.0 315.0

245.0

388.1

0 50

100

150

200

250

Relative Int. (%)

100 Cl D

D

57.1

F

N

N CH 2—CH 2O—C 4H 9 O

187.1 207.0

117.0

350

400

2-Hydroxyethylflurazepam-d4, butyl derivative

V-14-B-ii

D

D

50

300 292.1

C21H18D4ClFN2O2 MW: 392.89

277.1 264.0 249.1

319.1

392.1

0 50

100

150

200

250

300

350

400


100

Cl

50

73.1

F

N

288.0

V-14-C-i N CH2—CH2O—Si(CH3)3 O

183.1

117.1

2-Hydroxyethylflurazepam, trimethylsilyl derivative C20H22ClFN2O2Si MW: 404.94 389.1

273.1 360.1

245.0

404.1

0 50

100

150

Relative Int. (%)

100

200

Cl D

731.

D

F

N

117.1

300 292.1

V-14-C-ii

D

D

50

250

350

C20H18D4ClFN2O2Si MW: 408.96

277.1 187.1

450

2-Hydroxyethylflurazepam-d4, trimethylsilyl derivative

N CH2—CH2O—Si(CH3)3 O

400

364.1

249.1

393.1 408.2

0 50

100

150

200

250 m/z



300

350

400

450

318


Relative Int. (%)

100

389.1

2-Hydroxyethylflurazepam, t-butyldimethylsilyl derivative C23H28ClFN2O2Si MW: 447.02

50

F

73.1

V-14-D-i

Cl

N

N CH2CH2O—Si(CH3)2C(CH3)3 O

345.1

100.0

431.2


100

100

150

200

C23H24D4ClFN2O2Si MW: 451.04 73.1

300

350

400

V-14-D-ii

Cl D

D

D

F

D N

N CH2CH2O—Si(CH3)2C(CH3)3 O

100.0

349.1

435.2

0 50

100

150

200

250 m/z



450

393.1

2-Hydroxyethylflurazepam-d4, t-butyldimethylsilyl derivative

50

250

300

350

400

450

319

Figure V-15. Mass spectra of estazolam and its deuterated analogs (estazolam-d5).

Relative Int. (%)

100

Estazolam (CAS NO.29975-16-4)

259.1

Cl

C16H11ClN4 MW: 294.74

50

V-15-i

205.0 239.0

N

77.1

N

137.0

294.1

N

N

163.1


100

100

150

Estazolam-d5 (CAS NO.170082-16-3) C16H6D5ClN4 MW: 299.77

50

200

82.1

264.1

Cl

D

D

D

D

300 299.1

350

V-15-ii

210.0

D

137.0

250

N

N

N

N

244.0

163.0

0 50

100

150

200 m/z



250

300

350

320

Figure V-16. Mass spectra of alprazolam and its deuterated analogs (alprazolam-d5).

Relative Int. (%)

100

Alprazolam (CAS NO.28981-97-7)

Cl

C17H13ClN4 MW: 308.76

50

204.0

N

N

245.1

177.0

137.0

308.1

273.1

CH 3

N

N

77.0

279.0

V-16-i


100

100

150

Alprazolam-d5

250

Cl D

C17H8D5ClN4 MW: 313.80

209.1

D

D

50 82.1

200

D

137.0

N

V-16-ii

350

284.1 313.1

CH 3

N D

300

N

N

250.1

278.1

181.1

0 50

100

150

200 m/z



250

300

350

321

Figure V-17. Mass spectra of α-hydroxyalprazolam and its deuterated analogs (α-hydroxyalprazolam-d5): (A) TMSderivatized; (B) t-BDMS-derivatized.

Relative Int. (%)

100

α-Hydroxyalprazolam (CAS NO.37115-43-8),

381.1 Cl

trimethylsilyl derivative C20H21ClN4OSi MW: 396.95

50

V-17-A-i N

N

73.1

CH2OSi(CH3)3

154.1 173.1

N

396.1

N

207.0

346.1

293.1


100

100

150

200

250

300

α-Hydroxyalprazolam-d5 (CAS NO.136765-24-7),

73.1

D

D

D

154.1

175.7

450

V-17-A-ii

Cl


400 386.1

trimethylsilyl derivative

50

350

D

207.0

CH2OSi(CH3)3

N D

N

N

401.1

N

293.0

351.2

0 50

Relative Int. (%)

100

100

150

200

250 m/z

α-Hydroxyalprazolam,

C23H27ClN4OSi MW: 439.03 173.1

400

381.1

N

N

207.0

423.1


100

100

150

200

250

300

α-Hydroxyalprazolam-d5, t-butyldimethylsilyl derivative

50

175.6

207.0

D

N

N

N

428.2

0 50

100

150

200

250 m/z



450

CH2OSi(CH3)2C(CH3)3

N D

400 386.1

D

D

75.1

350

V-17-B-ii

Cl D


450

CH2OSi(CH3)2C(CH3)3

N N

75.1

350

V-17-B-i

Cl

t-butyldimethylsilyl derivative

50

300

300

350

400

450

322

Figure V-18. Mass spectra of α-hydroxytriazolam and its deuterated analogs (α-hydroxytriazolam-d4): (A) TMSderivatized; (B) t-BDMS-derivatized.

Relative Int. (%)

100

α-Hydroxytriazolam (CAS NO.37115-45-0), trimethylsilyl derivative C20H20Cl2N4OSi MW: 431.39

50

CH2OSi(CH3)3

N Cl

73.1

N

N

430.1

N

207.0

190.1

114.1

415.1

V-18-A-i

Cl

380.1

277.1

0 50

100

Relative Int. (%)

100

150

200

250

α-Hydroxytriazolam-d4,

350

D

C20H16D4Cl2N4OSi MW: 435.41

207.0

73.1

419.1

CH2OSi(CH3)3

N N Cl

N

192.1

114.1

450

D

D D

400

V-18-A-ii

Cl

trimethylsilyl derivative

50

300

434.1

N

281.1

384.1

0 50

Relative Int. (%)

100

100

150

α-Hydroxytriazolam,

200

250 m/z

400

450

Cl

V-18-B-i

C23H26Cl2N4OSi MW: 473.47

CH2OSi(CH3)2C(CH3)3

N

75.1

350

415.1


50

300

N Cl

207.0

190.0

N

N

380.1

457.2


100

100

150

200

α-Hydroxytriazolam-d4,

250

400

450

500

Cl

V-18-B-ii

C23H22D4Cl2N4OSi MW: 477.49

D

D

D

75.1

350

419.1


50

300

D

207.0

192.1

CH2OSi(CH3)2C(CH3)3

N N Cl

N

N

384.1

461.1

0 50

100

150

200

250

300 m/z



350

400

450

500

323

Figure V-19. Mass spectra of mianserin and its deuterated analogs (mianserin-d3).

Relative Int. (%)

100

193.0

Mianserin (CAS NO.24219-97-4)

V-19-i N

50

264.1

N

72.1

165.0

CH 3

220.1

C18H20N2 MW: 264.36

249.1

0 50

100

150

200

Relative Int. (%)

100

193.0

V-19-ii

250

Mianserin-d3 (CAS NO.81957-76-8)

N

267.1

50

300

C18H17D3N2 MW: 267.38

N

75.1

165.0

CD 3

220.1

249.1

0 50

100

150

200 m/z



250

300

324

Figure V-20. Mass spectra of methaqualone and its deuterated analogs (methaqualone-d7).

Relative Int. (%)

100

Methaqualone (CAS NO.72-44-6) C16H14N2O MW: 250.30

50

235.0

CH 3

N

V-20-i

N O H 3C

91.0 65.0

250.1

143.0


100

100

150

Methaqualone-d7 (CAS NO.136765-41-8)

CH 3

N

C16H7D7N2O MW: 257.34

50

200

N

250 242.1

V-20-ii

D D

O D 3C

98.1 70.0

300

D

257.1

D

143.0

0 50

100

150

200 m/z



250

300

325

Figure V-21. Mass spectra of haloperidol and its deuterated analogs (haloperidol-d4): (A) TMS-derivatized.

Relative Int. (%)

100

296.1

V-21-A-i

O

206.0

73.1

F

C

Haloperidol (CAS NO.52-86-8), trimethylsilyl derivative

OSi(CH3)3 N

50

C24H31ClFNO2Si MW: 448.05

103.0

Cl

430.1

0 50

100

150

200

250

Relative Int. (%)

100

300

350

296.1

V-21-A-ii 206.0

73.1

D

DO

D

D

F

50

C

400

450

500

Haloperidol-d4 (CAS NO.136765-35-0), trimethylsilyl OSi(CH3)3 derivative N

C24H27D4ClFNO2Si MW: 452.07

103.0

Cl

434.1

0 50

100

150

200

250

300 m/z



350

400

450

500

327

Summary of Drugs, Isotopic Analogs, and Chemical Derivatization Groups Included in Figure VI (Antidepressants) Compound

Isotopic analog


Figure #

Imipramine

d3

None (2)

VI-1

Desipramine

d3

None, acetyl, TCA, TFA, PFP, 4-CB, TMS, t-BDMS (16)

VI-2

Trimipramine

d3

None (2)

VI-3

Clomipramine

d3

None (2)

VI-4

Nortriptyline

d3


VI-5

Protriptyline

d3


VI-6

Doxepin

d3

None (2)

VI-7

Dothiepin

d3

None (2)

VI-8

Amitriptyline

d3

None (2)

Maprotiline

d3


VI-9


Figure VI — Antidepressant


VI-10

329

Appendix One — Figure VI Mass Spectra of Commonly Abused Drugs and Their Isotopically Labeled Analogs in Various Derivatization Forms — Antidepressants Figure VI-1. Mass spectra of imipramine and its deuterated analogs (imipramine-d3) .............................................................. 330 Figure VI-2. Mass spectra of desipramine and its deuterated analogs (desipramine-d3): (A) underivatized; (B) acetylderivatized; (C) TCA-derivatized; (D) TFA-derivatized; (E) PFP-derivatized; (F) 4-CB-derivatized; (G) TMS-derivatized; (H) t-BDMS-derivatized ............................................................................................................................................................... 331 Figure VI-3. Mass spectra of trimipramine and its deuterated analogs (trimipramine-d3) ......................................................... 334 Figure VI-4. Mass spectra of clomipramine and its deuterated analogs (clomipramine-d3) ...................................................... 335 Figure VI-5. Mass spectra of nortriptyline and its deuterated analogs (nortriptyline-d3): (A) underivatized; (B) acetylderivatized; (C) TCA-derivatized; (D) TFA-derivatized; (E) PFP-derivatized; (F) HFB-derivatized; (G) 4-CB-derivatized; (H) TMS-derivatized; (I) t-BDMS-derivatized ........................................................................................................................... 336 Figure VI-6. Mass spectra of protriptyline and its deuterated analogs (protriptyline-d3): (A) underivatized; (B) acetylderivatized; (C) TCA-derivatized; (D) TFA-derivatized; (E) PFP-derivatized; (F) HFB-derivatized; (G) 4-CB-derivatized; (H) TMS-derivatized; (I) t-BDMS-derivatized ............................................................................................................................ 339 Figure VI-7. Mass spectra of doxepin and its deuterated analogs (doxepin-d3) ......................................................................... 342 Figure VI-8. Mass spectra of dothiepin and its deuterated analogs (dothiepin-d3) .................................................................... 343 Figure VI-9. Mass spectra of amitriptyline and its deuterated analogs (amitriptyline-d3) ......................................................... 344 Figure VI-10. Mass spectra of maprotiline and its deuterated analogs (maprotiline-d3): (A) underivatized; (B) acetylderivatized; (C) TCA-derivatized; (D) TFA-derivatized; (E) PFP-derivatized; (F) HFB-derivatized; (G) 4-CB-derivatized; (H) TMS-derivatized; (I) t-BDMS-derivatized ............................................................................................................................ 345



330

Figure VI-1. Mass spectra of imipramine and its deuterated analogs (imipramine-d3).

Relative Int. (%)

100

58.1

234.1

VI-1-i N

85.1

50

CH 2

CH 2

CH 2 N

130.1

CH 3

Imipramine (CAS NO.50-49-7) C19H24N2 MW: 280.41

193.1

CH 3

220.1

280.2

165.1

0 50

100

Relative Int. (%)

100 61.1

150

200

250 234.1

VI-1-ii

Imipramine-d3 C19H21D3N2 MW: 283.43

N

50

88.1

CH 2

CH 2

CH 2 N

130.0

CD 3

300

193.0

CH 3

220.0

283.1

165.0

0 50

100

150

200 m/z



250

300

331

Figure VI-2. Mass spectra of desipramine and its deuterated analogs (desipramine-d3): (A) underivatized; (B) acetylderivatized; (C) TCA-derivatized; (D) TFA-derivatized; (E) PFP-derivatized; (F) 4-CB-derivatized; (G) TMSderivatized; (H) t-BDMS-derivatized. Relative Int. (%)

100

195.0

VI-2-A-i

234.1

Desipramine (CAS NO.50-47-5) C18H22N2 MW: 266.38

208.0

N

50

CH 2 –CH 2 –CH 2 –NH–CH 3

71.1

220.0

91.0

266.1

165.0

130.0

0 50

100

150

200

Relative Int. (%)

100

195.0

VI-2-A-ii CH 2 –CH 2 –CH 2 –NH–CD 3

74.1

Desipramine-d3 C18H19D3N2 MW: 269.40 269.1

220.0

165.0

130.0

91.0

300

208.0

N

50

250 234.1

0 50

100

150

200

250

300


100

208.0

VI-2-B-i

Desipramine, acetyl derivative

N

50

193.0

CH 2 –CH 2 –CH 2 –N–CH 3

114.0

C20H24N2O MW: 308.42

308.1

COCH 3

222.1

0 50

100

150

Relative Int. (%)

100

200

250

300

350

208.0

VI-2-B-ii

Desipramine-d3, acetyl derivative

N

50

193.0

CH 2 –CH 2 –CH 2 –N–CD 3

117.0

311.1

COCH 3

C20H21D3N2O MW: 311.44

222.1

0 50

100

150

200 m/z

Relative Int. (%)

100

250

300

350

Desipramine, trichloroacetyl derivative

208.1

VI-2-C-i N

50

CH 2 –CH 2 –CH 2 –N–CH 3

193.0

C20H21Cl3N2O MW: 411.75

COCCl 3

234.1

410.0

0 50

100

150

200

Relative Int. (%)

100

250

300

350

208.1

400

450

Desipramine-d3, trichloroacetyl derivative

VI-2-C-ii

C20H18D3Cl3N2O MW: 414.77

N

50 193.9

CH 2 –CH 2 –CH 2 –N–CD 3

234.1

COCCl 3

413.0

0 50

100

150

200

250 m/z



300

350

400

450

332

Figure VI-2. (Continued)

Relative Int. (%)

100

Desipramine, trifluoroacetyl derivative

208.1

VI-2-D-i

C20H21F3N2O MW: 362.39

N

50

193.1

CH 2 –CH 2 –CH 2 –N–CH 3

362.2

COCF 3

0 50

100

150

200

Relative Int. (%)

100

250

300

350

VI-2-D-ii

C20H18D3F3N2O MW: 365.41

N

50

193.1

400

Desipramine-d3, trifluoroacetyl derivative

208.1

CH 2 –CH 2 –CH 2 –N–CD 3

365.2

COCF 3

0 50

100

150

200

250

300

350

400


100

208.1

Desipramine, pentafluoropropionyl derivative

VI-2-E-i

C21H21F5N2O MW: 412.40

N

50

193.1

CH 2 –CH 2 –CH 2 –N–CH 3

119.0

412.2

COC 2 F 5

234.1

0 50

100

150

200

Relative Int. (%)

100

250

300

350

208.1

VI-2-E-ii 50

400

C21H18D3F5N2O MW: 415.41 415.2

N

193.1

CH 2 –CH 2 –CH 2 –N–CD 3 COC 2 F 5

234.1

119.0

450

Desipramine-d3, pentafluoropropionyl derivative

0 50

100

150

200

Relative Int. (%)

100

250 m/z

300

350

208.1

VI-2-F-i

400

Desipramine, 4-carboethoxyhexafluorobutyryl derivative C25H26F6N2O3 MW: 516.48

N

50

450

CH 2 –CH 2 –CH 2 –N–CH 3

193.1

516.2

CO(CF2)3COOC2H 5

234.1

322.1

0 50

100

150

200

Relative Int. (%)

100

250

300

350

400

208.1

450

500

550

Desipramine-d3, 4-carboethoxyhexafluorobutyryl derivative

VI-2-F-ii

C25H23D3F6N2O3 MW: 519.49

N

50

CH 2 –CH 2 –CH 2 –N–CD 3

193.1 234.1

325.1

CO(CF2)3COOC2H 5

519.2

0 50

100

150

200

250

300 m/z

350



400

450

500

550

333


Relative Int. (%)

100

73.1

50

116.1

Desipramine, trimethylsilyl derivative

234.1

VI-2-G-i

CH 2 –CH 2 –CH 2 –N–CH 3

208.1

102.1

C21H30N2Si MW: 338.56

N

193.1

143.1

Si(CH3)3

266.1

338.2

0 50

100

150

200

Relative Int. (%)

100

VI-2-G-ii 73.1

50

119.1

250

300

N

193.1

146.1

350

Desipramine-d3, trimethylsilyl derivative

234.1

CH 2 –CH 2 –CH 2 –N–CD 3

208.1

105.1

269.2

C21H27D3N2Si MW: 341.58

Si(CH3)3

341.2

0 50

100

Relative Int. (%)

100

150

200 m/z

250

300

102.1

Desipramine, t-butyldimethylsilyl derivative

VI-2-H-i

235.1

156.1

C24H36N2Si MW: 380.64

N

50 73.1

350

CH 2 –CH 2 –CH 2 –N–CH 3

193.1

Si(CH3)2C(CH3)3

129.1

380.2

0 50

100

Relative Int. (%)

100

150

200

250

300

350

105.1

Desipramine-d3, t-butyldimethylsilyl derivative

VI-2-H-ii 235.1 158.1

132.1

C24H33D3N2Si MW: 383.66

N

50 73.1

400

CH 2 –CH 2 –CH 2 –N–CD 3

193.1

Si(CH3)2C(CH3)3

383.3

0 50

100

150

200

250 m/z



300

350

400

334

Figure VI-3. Mass spectra of trimipramine and its deuterated analogs (trimipramine-d3).

Relative Int. (%)

100

58.1

VI-3-i

Trimipramine (CAS NO.739-71-9)

249.1

N

50

CH 2

84.0

99.1

CH 3 CH CH 2 N CH 3 CH 3

193.0

208.0

234.1

C20H26N2 MW: 294.43 294.1

165.0


100

100

150

200

250

61.1

VI-3-ii N

50

CH 2

87.1

102.1

CH

CH 2 N

CH 3

193.0

CD 3

208.0

300

249.1

Trimipramine-d3

234.1

C20H23D3N2 MW: 297.45

CH 3

297.2

165.0

0 50

100

150

200 m/z



250

300

335

Figure VI-4. Mass spectra of clomipramine and its deuterated analogs (clomipramine-d3).

Relative Int. (%)

100

58.1 N

Cl

85.1

50

CH 2 –CH 2 –CH 2 –N

165.0

130.0

Clomipramine (CAS NO.303-49-1) 269.0 C19H23ClN2 MW: 314.85

VI-4-i CH 3 CH 3

228.0

193.0

314.1


100

100

150

200

250

CH 2 –CH 2 –CH 2 –N

130.0

165.0

C19H20D3ClN2 MW: 317.87

CD 3 CH 3

193.0

350 Clomipramine-d3

VI-4-ii

N

Cl

88.1

50

300 269.0

61.1

227.0

317.1

0 50

100

150

200 m/z



250

300

350

336

Figure VI-5. Mass spectra of nortriptyline and its deuterated analogs (nortriptyline-d3): (A) underivatized; (B) acetyl-derivatized; (C) TCA-derivatized; (D) TFA-derivatized; (E) PFP-derivatized; (F) HFB-derivatized; (G) 4CB-derivatized; (H) TMS-derivatized; (I) t-BDMS-derivatized. Relative Int. (%)

100

44.1

Nortriptyline (CAS NO.72-69-5)

VI-5-A-i

C19H21N MW: 263.38

50 CH 2 –CH 2 –CH 2 –NH–CH 3

202.0 263.1


100

90

140

190

240

290

47.1

Nortriptyline-d3

VI-5-A-ii

C19H18D3N MW: 266.40

50 CH 2 –CH 2 –CH 2 –NH–CD 3

202.0 266.1

0 40

90

140

190

240

290


100

232.2

VI-5-B-i

50

C21H23NO MW: 305.41

217.1

CH 2 –CH 2 –CH 2 –N–CH 3

202.1

COCH 3

86.1

Nortriptyline, acetyl derivative

141.1

305.2

0 50

100

150

200

Relative Int. (%)

100

250 232.2

VI-5-B-ii

50

COCH 3

350 Nortriptyline-d3, acetyl derivative C21H20D3NO MW: 308.43

217.1

CH 2 –CH 2 –CH 2 –N–CD 3

89.1

300

202.1

141.1

308.2

0 50

100

150

200 m/z

Relative Int. (%)

100

250

300

232.1

Nortriptyline, trichloroacetyl derivative

VI-5-C-i 50

350

C21H20Cl3NO MW: 408.74

219.1 CH 2 –CH 2 –CH 2 –N–CH 3

91.0

191.0

117.0

COCCl 3

409.0

0 50

100

150

200

Relative Int. (%)

100

250

300

350

232.1

C21H17D3Cl3NO MW: 411.76

219.1 91.0

CH 2 –CH 2 –CH 2 –N–CD 3 COCCl 3

191.0

117.0

412.0

0 50

100

150

200

250 m/z



450

Nortriptyline-d3, trichloroacetyl derivative

VI-5-C-ii 50

400

300

350

400

450

337


Relative Int. (%)

100

232.1

Nortriptyline, trifluoroacetyl derivative

VI-5-D-i 50

C21H20F3NO MW: 359.39

217.1 91.1

CH 2 –CH 2 –CH 2 –N–CH 3 COCF 3

191.1

141.1

359.1

0 50

100

150

200

250

Relative Int. (%)

100

300

350

232.1

Nortriptyline-d3, trifluoroacetyl derivative

VI-5-D-ii 50

C21H17D3F3NO MW: 362.40

217.1 91.1

CH 2 –CH 2 –CH 2 –N–CD 3

191.1

141.1

400

COCF 3

362.2

0 50

100

150

200

250

300

350

400


100

232.1

Nortriptyline, pentafluoropropionyl derivative

VI-5-E-i 50

217.1 91.1

141.1

100

150

C22H20F5NO MW: 409.39

CH 2 –CH 2 –CH 2 –N–CH 3

204.1

COC 2 F 5

409.1

0 50

200

250

Relative Int. (%)

100

300

350

400

232.1

VI-5-E-ii 50

217.1 CH 2 –CH 2 –CH 2 –N–CD 3

204.1 91.1

450

Nortriptyline-d3, pentafluoropropionyl derivative C22H17D3F5NO MW: 412.41

COC 2 F 5

141.1

412.1

0 50

100

150

200

Relative Int. (%)

100

250 m/z

300

350

400

232.1

Nortriptyline, heptafluorobutyryl derivative

VI-5-F-i 217.1

50

CH 2 –CH 2 –CH 2 –N–CH 3

204.1 91.1

450

C23H20F7NO MW: 459.40

COC 3 F 7

169.0

459.1

0 50

100

150

200

250

Relative Int. (%)

100

300

350

400

232.1

219.1

CH 2 –CH 2 –CH 2 –N–CD 3

204.1 91.1

C23H17D3F7NO MW: 462.41

COC 3 F 7

169.0

462.2

0 50

100

150

200

250

300 m/z



500

Nortriptyline-d3, heptafluorobutyryl derivative

VI-5-F-ii 50

450

350

400

450

500

338


Relative Int. (%)

100

232.1

219.1

50 204.1 91.1

50

CO(CF2)3COOC2H 5

141.1

100

294.1

150

200

250


C26H25F6NO3 MW: 513.47

CH 2 –CH 2 –CH 2 –N–CH 3

0

513.2

300

350

400

450

500

VI-5-G-ii

C26H22D3F6NO3 MW: 516.49

219.1

50

CH 2 –CH 2 –CH 2 –N–CD 3

204.1 91.1

50

CO(CF2)3COOC2H 5

141.1

100

297.1

150

100

VI-5-H-i

200

250

516.2

300 m/z

350

400

116.1

450

500

C22H29NSi MW: 335.56

CH 2 –CH 2 –CH 2 –N–CH 3

73.1

202.1

Si(CH3)3

320.2

0 50

100

Relative Int. (%)

150

200

250

300

119.1

C22H26D3NSi MW: 338.57

50 CH 2 –CH 2 –CH 2 –N–CD 3

73.1

202.1

Si(CH3)3

323.2

0 100

150

Relative Int. (%)

100

200 m/z

250

300

158.2

50

C25H35NSi MW: 377.63

CH 2 –CH 2 –CH 2 –N–CH 3

73.1

Si(CH3)2C(CH3)3

102.1

0 50

100

150

Relative Int. (%)

200

250

320.2

300

377.2

350

161.2

50

C25H32D3NSi MW: 380.65

CH 2 –CH 2 –CH 2 –N–CD 3

73.1

Si(CH3)2C(CH3)3

323.2

105.1

379.3

0 100

150

200

250 m/z



400

Nortriptyline-d3, t-butyldimethylsilyl derivative

VI-5-I-ii

50

350

Nortriptyline, t-butyldimethylsilyl derivative

VI-5-I-i

100

350

Nortriptyline-d3, trimethylsilyl derivative

VI-5-H-ii

50

550

Nortriptyline, trimethylsilyl derivative

50

100

550

Nortriptyline-d3, 4-carboethoxyhexafluorobutyryl derivative

232.1

0

Relative Int. (%)

Nortriptyline, 4-carboethoxyhexafluorobutyryl derivative

VI-5-G-i

300

350

400

339

Figure VI-6. Mass spectra of protriptyline and its deuterated analogs (protriptyline-d3): (A) underivatized; (B) acetylderivatized; (C) TCA-derivatized; (D) TFA-derivatized; (E) PFP-derivatized; (F) HFB-derivatized; (G) 4-CB-derivatized; (H) TMS-derivatized; (I) t-BDMS-derivatized. Relative Int. (%)

100

191.0

Protriptyline (CAS NO.438-60-8)

VI-6-A-i

70.0

C19H21N MW: 263.38

50 CH 2 –CH 2 –CH 2 –NH–CH 3

165.0 263.1

0 50

100

150

200

Relative Int. (%)

100

250

191.0

300

Protriptyline-d3 (CAS NO.136765-50-9)

VI-6-A-ii

73.1

50

C19H18D3N MW: 266.39

CH 2 –CH 2 –CH 2 –NH–CD 3

165.0 266.1

0 50

100

150

200

250

300


100

191.2

Protriptyline, acetyl derivative

VI-6-B-i 50

C21H23NO MW: 305.41

CH 2 –CH 2 –CH 2 –N–CH 3 COCH 3

305.2

165.1

114.1

0 50

100

150

200

Relative Int. (%)

100

250

300

191.2

Protriptyline-d3, acetyl derivative

VI-6-B-ii

C21H20D3NO MW: 308.43

50 CH 2 –CH 2 –CH 2 –N–CD 3 COCH 3

165.1

117.1

350

308.2

0 50

100

150

Relative Int. (%)

100

200 m/z

250

300

191.1

350

Protriptyline, trichloroacetyl derivative

VI-6-C-i 50

CH 2 –CH 2 –CH 2 –N–CH 3

C21H20Cl3NO MW: 408.75

COCCl 3

165.0

409.0

0 50

100

150

200

Relative Int. (%)

100

250

300

350

191.1

400

450

Protriptyline-d3, trichloroacetyl derivative

VI-6-C-ii

C21H17D3Cl3NO MW: 411.77

50 CH 2 –CH 2 –CH 2 –N–CD 3 COCCl 3

165.0

412.0

0 50

100

150

200

250 m/z



300

350

400

450

340


Relative Int. (%)

100

Protriptyline, trifluoroacetyl derivative

191.1

VI-6-D-i

C21H20F3NO MW: 359.38

50


165.1

359.1

0 50

100

150

200

Relative Int. (%)

100

250

300

350

400

Protriptyline-d3, trifluoroacetyl derivative

191.1

VI-6-D-ii 50

C21H17D3F3NO MW: 362.40

CH 2 –CH 2 –CH 2 –N–CD 3 COCF 3

165.1

362.1

0 50

100

150

200

250

300

350

400


100

191.1

Protriptyline, pentafluoropropionyl derivative

VI-6-E-i 50

C22H20F5NO MW: 409.39

CH 2 –CH 2 –CH 2 –N–CH 3 COC 2 F 5

165.1

409.1

0 50

100

150

200

Relative Int. (%)

100

250

300

350

191.1

400

450

Protriptyline-d3, pentafluoropropionyl derivative

VI-6-E-ii 50

C22H17D3F5NO MW: 412.41

CH 2 –CH 2 –CH 2 –N–CD 3 COC 2 F 5

165.1

412.1

0 50

100

150

Relative Int. (%)

100

200

250 m/z

300

350

191.1

400

450

Protriptyline, heptafluorobutyryl derivative

VI-6-F-i 50

C23H20F7NO MW: 459.40

CH 2 –CH 2 –CH 2 –N–CH 3 COC 3 F 7

165.1

459.1

0 50

100

150

Relative Int. (%)

100

200

250

300

350

400

191.1

450

500

Protriptyline-d3, heptafluorobutyryl derivative

VI-6-F-ii

C23H17D3F7NO MW: 462.42

CH 2 –CH 2 –CH 2 –N–CD 3

50

COC 3 F 7

165.1

462.1

0 50

100

150

200

250

300 m/z



350

400

450

500

341


Relative Int. (%)

100

Protriptyline, 4-carboethoxyhexafluorobutyryl derivative

191.1

VI-6-G-i 50

C26H25F6NO3 MW: 513.47

CH 2 –CH 2 –CH 2 –N–CH 3 CO(CF2)3COOC2H 5

165.1

513.2

0 50

100

150

200

Relative Int. (%)

100

250

300

350

400

450

500

VI-6-G-ii 50

C26H22D3F6NO3 MW: 516.49

CH 2 –CH 2 –CH 2 –N–CD 3 CO(CF2)3COOC2H 5

165.1

516.2

0 50

100

150

Relative Int. (%)

100

550

Protriptyline-d3, 4-carboethoxyhexafluorobutyryl derivative

191.1

200

250

300 m/z

350

400

450

116.1

550

Protriptyline, trimethylsilyl derivative

VI-6-H-i 142.1

50

500

191.1

73.1

C22H29NSi MW: 335.56

CH 2 –CH 2 –CH 2 –N–CH 3 Si(CH3)3

320.2 335.2

0 50

100

Relative Int. (%)

100

150

200

250

300

119.1

350

Protriptyline-d3, trimethylsilyl derivative

VI-6-H-ii

C22H26D3NSi MW: 338.58

145.1

50

73.1

191.1

CH 2 –CH 2 –CH 2 –N–CD 3 Si(CH3)3

323.2 338.2

0 50

100

150

Relative Int. (%)

100

200 m/z

250

191.1

300

320.2

VI-6-I-i 50

350

Protriptyline, t-butyldimethylsilyl derivative

CH 2 –CH 2 –CH 2 –N–CH 3

158.1

C25H35NSi MW: 377.64

Si(CH3)2C(CH3)3

73.1 102.1

377.2

0 50

100

150

Relative Int. (%)

100

200

250

300

191.1 323.2

VI-6-I-ii 50

C25H32D3NSi MW: 380.66

Si(CH3)2C(CH3)3

105.1

380.2

0 50

100

150

200

250 m/z



400

Protriptyline-d3, t-butyldimethylsilyl derivative

CH 2 –CH 2 –CH 2 –N–CD 3

161.2

73.1

350

300

350

400

342

Figure VI-7. Mass spectra of doxepin and its deuterated analogs (doxepin-d3).

Relative Int. (%)

100

58.1

Doxepin (CAS NO.1668-19-5)

O

VI-7-i 50

CH–CH 2 –CH 2 –N

C19H21NO MW: 279.38

CH 3 CH 3

165.1

277.1


100

100

150

200

61.2

50


C19H18D3NO MW: 282.39

CH 3 CD 3

165.1

280.1

0 50

100

150

200 m/z



300

Doxepin-d3 (CAS NO.138387-16-3)

O

VI-7-ii

250

250

300

343

Figure VI-8. Mass spectra of dothiepin and its deuterated analogs (dothiepin-d3).

Relative Int. (%)

100

58.1

VI-8-i

Dothiepin (CAS NO.113-53-1) S

C19H21NS MW: 295.44

50 CH–CH 2 –CH 2 –N

CH 3 CH 3

202.1

295.1

221.0


100

100

150

200

250

61.2

VI-8-ii 50

300 Dothiepin-d3

S


C19H18D3NS MW: 298.46

CH 3 CD 3

202.1

221.0

298.1

0 50

100

150

200 m/z



250

300

344

Figure VI-9. Mass spectra of amitriptyline and its deuterated analogs (amitriptyline-d3).

Relative Int. (%)

100

58.1

Amitriptyline (CAS NO.50-48-6)

VI-9-i 50 CH–CH 2 –CH 2 –N

C20H23N MW: 277.40

CH 3 CH 3

202.0 215.0


100

100

150

200

250

61.1

300 Amitriptyline-d3

VI-9-ii 50


C20H20D3N MW: 280.42

CD 3 CH 3

202.0

218.0

0 50

100

150

200 m/z



250

300

345

FigureVI-10 Mass spectra of maprotiline and its deuterated analogs (maprotiline-d3): (A) underivatized; (B) acetylderivatized; (C) TCA-derivatized; (D) TFA-derivatized; (E) PFP-derivatized; (F) HFB-derivatized; (G) 4-CBderivatized; (H) TMS-derivatized; (I) t-BDMS-derivatized. Relative Int. (%)

100

44.1

Maprotiline (CAS NO.10262-69-8)

VI-10-A-i

C20H23N MW: 277.40

50

CH 2 –CH 2 –CH 2 –NH–CH 3

70.1

277.1

203.1

178.1


100

90 47.1

50

140

190

240

290

Maprotiline-d3 (CAS NO.136765-39-4)

VI-10-A-ii

C20H20D3N MW: 280.42

73.1

280.1

CH 2 –CH 2 –CH 2 –NH–CD 3

203.0

178.0

0 40

90

140

190

240

290


100

Maprotiline, acetyl derivative

291.2

VI-10-B-i 218.1

50

CH 2 –CH 2 –CH 2 –N–CH 3

C22H25NO MW: 319.44

191.1

COCH 3

178.1

100.1

319.2

0 50

100

150

200

250

Relative Int. (%)

100

300

Maprotiline-d3, acetyl derivative

294.2

VI-10-B-ii 50

CH 2 –CH 2 –CH 2 –N–CD 3

218.1

C22H22D3NO MW: 322.46

191.1

COCH 3

350

178.1

103.1

322.2

0 50

Relative Int. (%)

100

100

150

200 m/z 191.0

Maprotiline, trichloroacetyl derivative C22H22Cl3NO MW: 422.77

50

95.5

250

300

VI-10-C-i

203.0

350

393.0

CH 2 –CH 2 –CH 2 –N–CH 3 COCCl 3

178.0 138.0

276.0

423.0


100

100

150

200

C22H19D3Cl3NO MW: 425.79

350

VI-10-C-ii

203.0

400 396.0

COCCl 3

139.5

279.1

426.1

0 50

100

150

200

250 m/z



450

CH 2 –CH 2 –CH 2 –N–CD 3

178.0 95.5

300

191.0

Maprotiline-d3, trichloroacetyl derivative

50

250

300

350

400

450

346


Relative Int. (%)

100

Maprotiline, trifluoroacetyl derivative

VI-10-D-i

191.1

C22H22F3NO MW: 373.41

50

345.1


203.1 140.1

373.2


100

100

150

200

250

300

VI-10-D-ii

191.1

C22H19D3F3NO MW: 376.43

CH 2 –CH 2 –CH 2 –N–CD 3

0 100

COCF 3

203.1

143.1

50

400

348.2

Maprotiline-d3, trifluoroacetyl derivative

50

350

376.2

150

200

250

300

350

400


100

395.1

Maprotiline, pentafluoropropionyl derivative

VI-10-E-i

191.1

C23H22F5NO MW: 423.42

50

CH 2 –CH 2 –CH 2 –N–CH 3 COC 2 F 5

203.1

119.0

423.1


100

100

150

200

250

350

400

450

398.1

Maprotiline-d3, pentafluoropropionyl derivative

VI-10-E-ii

191.1

C23H19D3F5NO MW: 426.44

50

300

CH 2 –CH 2 –CH 2 –N–CD 3 COC 2 F 5

203.1

119.0

426.2

0 50

Relative Int. (%)

100

100

150

Maprotiline, heptafluorobutyryl derivative

200

250 m/z

350

VI-10-F-i

191.1

C24H22F7NO MW: 473.43

50

300

400

450

445.1

CH 2 –CH 2 –CH 2 –N–CH 3 COC 3 F 7

203.1

473.1


100

100

150

200

250

300

400

450

VI-10-F-ii

191.1

C24H19D3F7NO MW: 476.44

CH 2 –CH 2 –CH 2 –N–CD 3

203.1

COC 3 F 7

476.2

0 50

100

150

200

250

300 m/z



500

448.2

Maprotiline-d3, heptafluorobutyryl derivative

50

350

350

400

450

500

347


Relative Int. (%)

100

Maprotiline, 4-carboethoxyhexafluorobutyryl derivative

499.2

C27H27F6NO3 MW: 527.50

50

VI-10-G-i

191.1

CH 2 –CH 2 –CH 2 –N–CH 3

218.1

CO(CF2)3COOC2H 5

178.1

527.2


100

100

150

Maprotiline-d3, 4-carboethoxyhexafluorobutyryl derivative

200

300

350

400

450

500

550 502.2

191.1

C27H24D3F6NO3 MW: 530.52

50

250

VI-10-G-ii CH 2 –CH 2 –CH 2 –N–CD 3

218.1

CO(CF2)3COOC2H 5

178.1

530.2

0 50

100

150

Relative Int. (%)

100

200

250

300 m/z

350

400

450

116.1

500

550

Maprotiline, trimethylsilyl derivative

VI-10-H-i 50

C23H31NSi MW: 349.59

CH 2 –CH 2 –CH 2 –N–CH 3 Si(CH3)3

73.1 191.1

349.2

277.2

0 50

100

150

Relative Int. (%)

100

200

250

300

350

119.1

VI-10-H-ii 50

C23H28D3NSi MW: 352.60

CH 2 –CH 2 –CH 2 –N–CD 3

73.1

Si(CH3)3

191.1

100

150

352.2

280.2

0 50

400

Maprotiline-d3, trimethylsilyl derivative

200

250

300

350

400


100

334.2

VI-10-I-i 102.1

50

Maprotiline, t-butyldimethylsilyl derivative

158.1 191.1

C26H37NSi MW: 391.66

CH 2 –CH 2 –CH 2 –N–CH 3

73.1

Si(CH3)2C(CH3)3

306.1 391.3

0 50

100

Relative Int. (%)

100

150

200

250

300 337.2

VI-10-I-ii 105.1

50

161.2

350

191.1

Maprotiline-d3, t-butyldimethylsilyl derivative C26H34D3NSi MW: 394.68

CH 2 –CH 2 –CH 2 –N–CD 3

73.1

400

309.2

Si(CH3)2C(CH3)3

394.3

0 50

100

150

200

250 m/z



300

350

400

349

Summary of Drugs, Isotopic Analogs, and Chemical Derivatization Groups Included in Figure VII (Others) Compound

Isotopic analog


Figure #

Diphenhydramine

d3

None (2)

VII-1

Cotinine

d3

None (2)

VII-2

Nicotine

d4

None (2)

VII-3

5-α-Estran-3α-ol-17-one d3

None, acetyl, TMS (6)

VII-4

5-β-Estran-3α-ol-17-one d3

None, acetyl, TMS (6)

VII-5

Stanozolol

d3

None, acetyl, [TMS]2, t-BDMS (8)

VII-6

3-Hydroxystanozolol

d3

[TMS]2, [t-BDMS]2 (4)

VII-7

Promethazine

d3

None (2)

VII-8

Chlorpromazine

d3

None (2)

VII-9

Acetaminophen

d4

None, [acetyl]2, TCA, TFA, PFP, HFB, 4-CB, TMS, [TMS]2, t-BDMS, [t-BDMS]2 (22)

VII-10

Clonidine

d4

None, acetyl, [acetyl]2, TMS, [TMS]2, [t-BDMS]2 (12)

VII-11

Chloramphenicol

d5

None, [acetyl]2, TMS, [TMS]2 (8)

VII-12

Melatonin

d7

None, acetyl, TFA, PFP, HFB, TMS (12)

VII-13


Figure VII — Others


351

Appendix One — Figure VII Mass Spectra of Commonly Abused Drugs and Their Isotopically Labeled Analogs in Various Derivatization Forms — Others Figure VII-1. Mass spectra of diphenhydramine and its deuterated analogs (diphenhydramine-d3) ......................................... 352 Figure VII-2. Mass spectra of cotinine and its deuterated analogs (cotinine-d3) ....................................................................... 353 Figure VII-3. Mass spectra of nicotine and its deuterated analogs (nicotine-d4) ....................................................................... 354 Figure VII-4. Mass spectra of 5-α-estran-3α-ol-17-one and its deuterated analogs (5-α-estran-3α-ol-17-one-d3): (A) underivatized; (B) acetyl-derivatized; (C) TMS-derivatized ....................................................................................................... 355 Figure VII-5. Mass spectra of 5-β-estran-3α-ol-17-one and its deuterated analogs (5-β-estran-3α-ol-17-one-d3): (A) underivatized; (B) acetyl-derivatized; (C) TMS-derivatized ....................................................................................................... 356 Figure VII-6. Mass spectra of stanozolol and its deuterated analogs (stanozolol-d3): (A) underivatized; (B) acetylderivatized; (C) [TMS]2-derivatized. (D) t-BDMS-derivatized ................................................................................................... 357 Figure VII-7. Mass spectra of 3-hydroxystanozolol and its deuterated analogs (3-hydroxystanozolol-d3): (A) [TMS]2derivatized; (B) [t-BDMS]2-derivatized ....................................................................................................................................... 359 Figure VII-8. Mass spectra of promethazine and its deuterated analogs (promethazine-d3) ..................................................... 360 Figure VII-9. Mass spectra of chlorpromazine and its deuterated analogs (chlorpromazine-d3) ............................................... 361 Figure VII-10. Mass spectra of acetaminophen and its deuterated analogs (acetaminophen-d4): (A) underivatized; (B) [acetyl]2-derivatized; (C) TCA-derivatized; (D) TFA-derivatized; (E) PFP-derivatized; (F) HFB-derivatized; (G) 4-CBderivatized; (H) TMS-derivatized; (I) [TMS]2-derivatized; (J) t-BDMS-derivatized; (K) [t-BDMS]2-derivatized ................... 362 Figure VII-11. Mass spectra of clonidine and its deuterated analogs (clonidine-d4): (A) underivatized; (B) acetylderivatized; (C) [acetyl]2-derivatized; (D) TMS-derivatized; (E) [TMS]2-derivatized; (F) [t-BDMS]2-derivatized ................. 366 Figure VII-12. Mass spectra of chloramphenicol and its deuterated analogs (chloramphenicol-d5): (A) underivatized; (B) [acetyl]2-derivatized; (C) TMS-derivatized; (D) [TMS]2-derivatized ......................................................................................... 368 Figure VII-13. Mass spectra of melatonin and its deuterated analogs (melatonin-d7): (A) underivatized; (B) acetylderivatized; (C) TFA-derivatized; (D) PFP-derivatized; (E) HFB-derivatized; (F) TMS-derivatized ....................................... 370



352

Figure VII-1. Mass spectra of diphenhydramine and its deuterated analogs (diphenhydramine-d3).

Relative Int. (%)

100

58.1

Diphenhydramine (CAS NO.58-73-1),

VII-1-i

CH 3

50

O

73.1

165.1 227.1


C17H21NO MW: 255.35

N CH 3

100

150

200

250

61.1

Diphenhydramine-d3

CH 3

VII-1-ii O

C17H18D3NO MW: 258.37

N CD 3

50 76.1

300

165.1 230.1

0 50

100

150

200 m/z



250

300

353

Figure VII-2. Mass spectra of cotinine and its deuterated analogs (cotinine-d3).

Relative Int. (%)

100

98.0

Cotinine (CAS NO.486-56-6)

VII-2-i

N N

50

176.1

119.0

78.0

C10H12N2O MW: 176.21

O

CH 3

147.0

0 50

100

Relative Int. (%)

100

150 101.1

Cotinine-d3 (CAS NO.66269-66-7)

VII-2-ii

N

N

50 118.0

78.0

200

C10H9D3N2O MW: 179.23

O

CD 3

179.1 147.0

0 50

100

150 m/z



200

354

Figure VII-3. Mass spectra of nicotine and its deuterated analogs (nicotine-d4).

Relative Int. (%)

100

84.1

Nicotine (CAS NO.54-11-5)

VII-3-i

C10H14N2 MW: 162.23

N N

50

CH 3

133.1 162.1 119.0

92.0

65.1

0 50

100

Relative Int. (%)

100

150

200 Nicotine-d4

84.1

VII-3-ii

D

C10H10D4N2 MW: 166.20

D

N

50

D N D CH 3

136.1 68.1

96.1

166.1

123.1

0 50

100

150 m/z



200

355

Figure VII-4. Mass spectra of 5-α-estran-3α-ol-17-one and its deuterated analogs (5-α-estran-3α-ol-17-one-d3): (A) underivatized; (B) acetyl-derivatized; (C) TMS-derivatized. Relative Int. (%)

100

5-α−Estran-3α−ol-17-one

VII-4-A-i

C18H28O2 MW: 276.41

50 79.1

55.1 67.1

91.1

202.2 187.2

232.2

131.1 146.1 159.2

105.1

276.2

H 3C O

HO

214.2

258.2

H


100

100

67.1

79.1

200

250

93.1

205.2

C18H25D3O2 MW: 279.43

217.2

190.2

D HO

148.1 162.2

107.1

55.1

300 279.3

H 3C O

5-α−Estran-3α−ol-17-one-d3

VII-4-A-ii

50

150

261.2

D D

134.1

235.2

0 50

100

150

200

250

300


100

5-α−Estran-3α−ol-17-one, acetyl derivative 79.1

50

91.1

C20H30O3 MW: 318.45 119.1

146.1

258.2

VII-4-B-i

H 3C O

202.1

187.1

H3COCO

214.2

H

240.1

318.2

0 50

100

Relative Int. (%)

100 93.1 79.1

150

200

5-α−Estran-3α−ol-17-one-d3, acetyl derivative C20H27D3O3 MW: 321.47 149.1 122.1

50

250

VII-4-B-ii

205.2

300

350

261.2 H 3C O

217.2

190.2

D H3COCO

243.2

D D

321.2

0 50

100

150

Relative Int. (%)

100

VII-4-C-i 75.1

50

129.1 91.1

200 m/z

250

300

5-α−Estran-3α−ol-17-one, trimethylsilyl derivative

H 3C O

C21H36O2Si MW: 348.59 155.1

350

333.2

258.2 201.2

230.2

3(H3C)SiO

348.3

H


100

100 75.1

150

VII-4-C-ii 130.1

50 93.1

200

250

5-α−Estran-3α−ol-17-one-d3, trimethylsilyl derivative

350 H 3C O

261.2

C21H33D3O2Si MW: 351.61

400

336.3

D

204.2

157.1

300

233.2

3(H3C)SiO

D D

351.3

0 50

100

150

200

250 m/z



300

350

400

356

Figure VII-5. Mass spectra of 5-β-estran-3α-ol-17-one and its deuterated analogs (5-β-estran-3α-ol-17-one-d3): (A) underivatized; (B) acetyl-derivatized; (C) TMS-derivatized. Relative Int. (%)

100

5-β−Estran-3α−ol-17-one C18H28O2 91.1 MW: 276.41 79.1 67.1 55.1

50

H 3C O

VII-5-A-i 145.1

105.1

160.1

276.2

232.2

202.2

214.2

187.2

HO

H

131.1

258.2


100

100

150

5-β−Estran-3α−ol-17-one-d3 C18H25D3O2 MW: 279.43 79.1 67.1 55.1

50

200

250

204.2

VII-5-A-ii

235.2 217.2

148.1 161.2

91.1

279.3

HO

190.2

107.1 120.1

300 H 3C O

D

261.2

D D

0 50

100

150

200

250

300


100

91.1

79.1

105.1 VII-5-B-i 145.1

202.2 214.1

187.1

258.2

119.1

50

5-β−Estran-3α−ol-17-one, acetyl derivative H 3C O C20H30O3 MW: 318.45

230.2 274.2

H3COCO

318.2

H

0 50

100

150

Relative Int. (%)

100 107.1

148.1

120.1

250 204.2

VII-5-B-ii

93.1

79.1

200

300

350

5-β−Estran-3α−ol-17-one-d3, acetyl derivative

217.2 190.2

261.2

50 233.2

H 3C O

C20H27D3O3 MW: 321.47 H3COCO

277.2

D

321.2 D D

0 50

100

150

200 m/z

Relative Int. (%)

100

H 3C O

VII-5-C-i

75.1

250

300

258.2

5-β−Estran-3α−ol-17-one, trimethylsilyl derivative

216.2

129.1

50

91.1

105.1

3(H3C)SiO

350

C21H36O2Si MW: 348.59

333.2 H

230.2 349.3


100

100 75.1

150

H 3C O

VII-5-C-ii 130.1

50

200

250

300

217.2

350

5-β−Estran-3α−ol-17 one-d3, trimethylsilyl derivative

261.2

C21H33D3O2Si MW: 351.61

3(H3C)SiO

93.1

D

107.1

D D

400

336.3

233.2

351.3

0 50

100

150

200

250 m/z



300

350

400

357

Figure VII-6. Mass spectra of stanozolol and its deuterated analogs (stanozolol-d3): (A) underivatized; (B) acetylderivatized; (C) [TMS]2-derivatized. (D) t-BDMS-derivatized.

Relative Int. (%)

100

96.1

Stanozolol (CAS NO.10418-03-8) C21H32N2O MW: 328.49

H 3C H 3C

133.1 119.1

147.1

VII-6-A-i

328.2

N HN

50 55.1

OH CH 3

H

175.1

257.2

270.2

207.0

295.2

0 50

100

Relative Int. (%)

100

150

200

250

Stanozolol-d3 (CAS NO.88247-87-4)

96.1

H 3C

C21H29D3N2O MW: 331.51

50 119.1

H 3C

300

OH CD 3

350

VII-6-A-ii 331.2

N HN

133.1 147.1

55.1

H

175.1

257.2

270.2

207.0

298.2

0 50

100

150

Relative Int. (%)

100

200 m/z

250

138.1

H 3C H 3C

96.1

300

OCOCH3 CH 3

350

Stanozolol, acetyl derivative

VII-6-B-i

C23H34N2O2 MW: 370.53 370.2

N HN

50

257.2

H

71.1

147.1

175.1

327.2

313.2

215.2

0 50

100

150

Relative Int. (%)

100

200

250

138.1

H 3C H 3C

96.1

300 OCOCH3 CD 3

350

VII-6-B-ii

C23H31D3N2O2 MW: 373.55 373.3

N HN

50 147.1

74.1

257.2

H

175.2

330.2

313.2

218.2

400

Stanozolol-d3, acetyl derivative

0 50

100

150

200

250

300

350

400


100

VII-6-C-i

143.1 H 3C H 3C

50

Stanozolol, di-trimethylsilyl derivative

OSi(CH3)3 CH 3

C27H48N2OSi2 MW: 472.85

N (H3C)3SiN

73.1

H

168.1

472.3

342.2


100

100

VII-6-C-ii

150

200

250

300

146.1 H 3C H 3C

400

450

C27H45D3N2OSi2 MW: 475.87

H

168.1

500

Stanozolol-d3, di-trimethylsilyl derivative

OSi(CH3)3 CD 3

N (H3C)3SiN

73.1

50

350

475.3 343.2

0 50

100

150

200

250

300 m/z



350

400

450

500

358

Figure VII-6. (Continued)

Relative Int. (%)

100

Stanozolol, t-butyldimethylsilyl derivative

VII-6-D-i H 3C

C27H46N2OSi MW: 442.75 73.1

50

H 3C

386.3

OSi(CH3)2C(CH3)3 CH 3

N HN

152.1

H

358.2

442.3


100

100

150

Stanozolol-d3, t-butyldimethylsilyl derivative

250

300

350

400

450

389.3

VII-6-D-ii

H 3C H 3C

C27H43D3N2OSi MW: 445.78 73.1

50

200


N HN

152.1

H

445.4

361.3

0 50

100

150

200

250 m/z



300

350

400

450

359

Figure VII-7. Mass spectra of 3-hydroxystanozolol and its deuterated analogs (3-hydroxystanozolol-d3): (A) [TMS]2derivatized. (B) [t-BDMS]2-derivatized.

Relative Int. (%)

100

254.1

3’-Hydroxystanozolol (CAS NO.125709-39-9), di-trimethylsilyl derivative

73.1

C27H48N2O2Si2 MW: 488.85

50

147.1

H 3C HO H C 3

VII-7-A-i

OSi(CH3)3 CH 3

473.3

N N

488.4

(H3C)3Si

207.0

H

417.2

448.3

0 50

100

Relative Int. (%)

100

150

200

250

3’-Hydroxystanozolol-d3 (CAS NO.170082-17-4), di-trimethylsilyl derivative

73.1

C27H45D3N2O2Si2 MW: 491.87

50

300

350

400

450

254.1

500

476.3 H 3C

VII-7-A-ii

HO H C 3

OSi(CH3)3 CD 3

491.3

N N

147.1

(H3C)3Si

198.1

H

417.3

451.3

0 50

100

150

200

250

300

350

400

450

500


100

VII-7-B-i 73.1 147.1

50

515.4

3’-Hydroxystanozolol, di-t-butyldimethylsilyl derivative

H 3C HO H C 3

C33H60N2O2Si2 MW: 573.01

N N (H3C)3C(H3C)2Si

OSi(CH3)2C(CH3)3 CH 3

459.3

H

497.3

572.5


100

100

150

VII-7-B-ii 73.1

50

147.1

200

250

300

3’-Hydroxystanozolol-d3, di-t-butyldimethylsilyl derivative

350

400 H 3C

HO H C 3

450

500

550

600

518.4


N

C33H57D3N2O2Si2 N MW: 576.03 (H3C)3C(H3C)2Si

462.3

H

500.4

575.4

0 50

100

150

200

250

300

350 m/z



400

450

500

550

600

360

Figure VII-8. Mass spectra of promethazine and its deuterated analogs (promethazine-d3).

Relative Int. (%)

100

72.1

CH 3

50

Promethazine (CAS NO.60-87-7)

VII-8-i

CH 3 CH 2–CH–N CH 3 N

C17H20N2S MW: 284.42

199.0

S

167.1

213.0

284.1


100

100

150

75.1

200

300

CD 3 CH 2–CH–N CH 3 N S

350 Promethazine-d3

VII-8-ii

CH 3

50

250

C17H17D3N2S MW: 287.44

199.0 167.1

213.0

287.1

0 50

100

150

200 m/z



250

300

350

361

Figure VII-9. Mass spectra of chlorpromazine and its deuterated analogs (chlorpromazine-d3).

Relative Int. (%)

100

58.1

VII-9-i

Chlorpromazine (CAS NO.50-53-3)

S Cl

50 86.1

C17H19ClN2S MW: 318.86

N CH 3 CH 2 –CH 2 –CH 2 –N CH 3

196.0

318.0

272.0

232.0


100

100

150

200

250

61.1

VII-9-ii 50 89.1

350

Chlorpromazine-d3 (CAS NO.136765-28-1)

S Cl

300

C17H16D3ClN2S MW: 321.88

N CD 3 CH 2 –CH 2 –CH 2 –N CH 3

196.0

232.0

321.1

272.0

0 50

100

150

200 m/z



250

300

350

362

Figure VII-10. Mass spectra of acetaminophen and its deuterated analogs (acetaminophen-d4): (A) underivatized; (B) [acetyl]2-derivatized; (C) TCA-derivatized; (D) TFA-derivatized; (E) PFP-derivatized; (F) HFB-derivatized; (G) 4CB-derivatized; (H) TMS-derivatized; (I) [TMS]2-derivatized; (J) t-BDMS-derivatized; (K) [t-BDMS]2-derivatized.

Relative Int. (%)

100

Acetaminophen (CAS NO.103-90-2)

109.0

VII-10-A-i

C8H9NO2 MW: 151.16

NH–C–CH 3 O

50

HO

151.0

80.0

53.0

0 50

100

150

Relative Int. (%)

100

200

112.0

VII-10-A-ii

Acetaminophen-d4 D

D

50

C8H5D4NO2 MW: 155.19

NH–C–CH 3 O

HO D

83.0

154.0

D

55.0

0 50

100

150

200


100

109.1

COCH 3 N–C–CH 3

C12H13NO4 MW: 235.24

151.0

O

50

Acetaminophen, di-acetyl derivative

VII-10-B-i

H3COCO

193.0 80.1

235.0

0 50

100

Relative Int. (%)

100 D H3COCO

D

D

C12H9D4NO4 MW: 239.26

197.1 84.1

50

239.1

100

100

150 m/z

200

250

Acetaminophen, trichloroacetyl derivative

108.0 COCCl 3

VII-10-C-i

O

HO

252.9

134.0

80.0

50

C10H8Cl3NO3 MW: 296.53

N–C–CH 3

50

294.9 223.9

0 100


Acetaminophen-d4, di-acetyl derivative

155.1

O

50

250

VII-10-B-ii

N–C–CH 3

0

Relative Int. (%)

200

113.1

COCH 3

D

150

150

200

250

112.0

VII-10-C-ii

D

50

D

O D

138.0

84.0

C10H4D4Cl3NO3 MW: 300.56 298.9

227.0

100

150

200 m/z



256.9

D

0 50

Acetaminophen-d4, trichloroacetyl derivative

COCCl 3 N–C–CH 3

HO

300

250

300

363


Relative Int. (%)

100

Acetaminophen, trifluoroacetyl derivative

108.0

VII-10-D-i

COCF 3

205.0

N–C–CH 3

50

HO

69.0

C10H8F3NO3 MW: 247.17

O

247.0

80.1

0 50

100

150

Relative Int. (%)

100

200

112.1

VII-10-D-ii

D

D

50

300

Acetaminophen-d4, trifluoroacetyl derivative

COCF 3 N–C–CH 3

209.0

C10H4D4F3NO3 MW: 251.19

O

HO D

69.0

250

D

251.0

84.1

0 50

100

150

200

250

300


100

108.0

COC 2 F 5

VII-10-E-i

N–C–CH 3

50

O

HO

208.0

0 50

100

Relative Int. (%)

100

150

200

112.1

VII-10-E-ii

D

D

50

Relative Int. (%)

Acetaminophen-d4, pentafluoropropionyl derivative

COC 2 F 5

259.0

D

C11H4D4F5NO3 MW: 301.20

301.0 212.0

0 100

VII-10-F-i

350

119.0

84.1

100

300

O D

50

250

N–C–CH 3

HO

69.1

C11H8F5NO3 MW: 297.18

297.0

119.0

80.1

69.0

Acetaminophen, pentafluoropropionyl derivative

255.0

150

200 m/z

250

300

108.0

Acetaminophen, heptafluorobutyryl derivative

COC 3 F 7 N–C–CH 3

50

305.0

O

HO

350

C12H8F7NO3 MW: 347.19

347.0 69.0

134.0

169.0

0 50

100

Relative Int. (%)

100

VII-10-F-ii

150

200

300

350

112.1 D

50

D

309.0

O D

138.1

400

Acetaminophen-d4, heptafluorobutyryl derivative

COC 3 F 7 N–C–CH 3

HO

69.0

250

D

351.0

C12H4D4F7NO3 MW: 351.21

169.0

0 50

100

150

200

250 m/z



300

350

400

364


Relative Int. (%)

100

108.0 CO(CF2)3COOC2H 5

HO

359.0 401.0

80.1

50

134.0

100

Relative Int. (%)

100

C15H13F6NO5 MW: 401.26

O

243.0

0 150

200

250

300

350

400

112.0 D

50

D

O

HO D

84.1

50

D

100

405.0 247.1

150

200

250 m/z

Acetaminophen, trimethylsilyl derivative 73.1

50

C15H9D4F6NO5 MW: 405.28

363.0

138.1

100

VII-10-G-ii

N–C–CH 3

450

Acetaminophen-d4, 4-carboethoxyhexafluorobutyryl derivative

CO(CF2)3COOC2H 5

0

Relative Int. (%)

VII-10-G-i

N–C–CH 3

50

Acetaminophen, 4-carboethoxyhexafluorobutyryl derivative

C11H17NO2Si MW: 223.34

300

450

223.1

VII-10-H-i

N–C–CH 3 O

HO

400

181.1

166.0

Si(CH3)3

350

208.1 106.1

93.0

55.1

150.0

0 50

100

Relative Int. (%)

100 73.1

150

Acetaminophen-d4, trimethylsilyl derivative C11H13D4NO2Si MW: 227.37

50 55.1

D

D

Si(CH3)3

227.1

VII-10-H-ii

O

HO D

250

170.1

N–C–CH 3

D

212.0

110.0

93.1

200 185.1

147.1

0 50

100

Relative Int. (%)

100

150 m/z

Acetaminophen, di-trimethylsilyl derivative

50

73.1

200

206.1

Si(CH3)3

280.1 295.1

VII-10-I-i

N–C–CH 3

C14H25NO2Si2 MW: 295.52

250

O (H3C)3SiO

166.1

116.1

181.1

223.1 237.1

0 50

100

Relative Int. (%)

100

150

Acetaminophen-d4, di-trimethylsilyl derivative 73.1

50

C14H21D4NO2Si2 MW: 299.55

D

200 D

210.1

Si(CH3)3 N–C–CH 3

D

299.2

D

170.1

116.1

300 284.1

VII-10-I-ii

O (H3C)3SiO

250

185.1

227.1 241.1

0 50

100

150

200 m/z



250

300

365


Relative Int. (%)

100

Acetaminophen, t-butyldimethylsilyl derivative

208.0 Si(CH3)2C(CH3)3

VII-10-J-i

N–C–CH 3

50 73.1

C14H23NO2Si MW: 265.42

O

HO

265.1 166.0

106.1

250.0

0 50

100

150

200

Relative Int. (%)

100

VII-10-J-ii 50

D

D

D

269.1

73.1

170.0

110.1

100

212.1

Si(CH3)2C(CH3)3 O

D

50

300 Acetaminophen-d4, t-butyldimethylsilyl derivative

N–C–CH 3

HO

0

250

C14H19D4NO2Si MW: 269.45

254.1

150

200

250

300


100

Acetaminophen, di-t-butyldimethylsilyl derivative C20H37NO2Si2 MW: 379.68 73.1

50

Si(CH3)2C(CH3)3

VII-10-K-i

N–C–CH 3 O

248.1

(H3C)3C(H3C)2SiO

157.1

206.1

192.1

322.2

308.1

364.2

379.2


100

100

150

Acetaminophen-d4, di-t-butyldimethylsilyl derivative

50

C20H33D4NO2Si2 MW: 383.71 73.1

200 D

D

250

Si(CH3)2C(CH3)3 N–C–CH 3

300

VII-10-K-ii

100

157.1

D

252.2

D

210.1

196.1

312.2

150

383.2 368.2

200

250 m/z



400

O (H3C)3C(H3C)2SiO

0 50

350 326.2

300

350

400

366

Figure VII-11. Mass spectra of clonidine and its deuterated analogs (clonidine-d4): (A) underivatized; (B) acetylderivatized; (C) [acetyl]2-derivatized; (D) TMS-derivatized; (E) [TMS]2-derivatized; (F) [t-BDMS]2-derivatized.

Relative Int. (%)

100

229.0

Clonidine (CAS NO.4205-90-7)

H N

C9H9Cl2N3 MW: 230.09

50

N

N H

75.0

108.9

123.9

VII-11-A-i

Cl

171.9

Cl

194.0

144.9


100

100

150

Clonidine-d4

D D D D

C9H5D4Cl2N3 MW: 234.11

50

108.9

75.0

123.9

H N

200

250 233.0

VII-11-A-ii

Cl N

N H

Cl

171.9

198.0

144.9

0 50

100

Relative Int. (%)

100

200

250

236.0

194.0

H N

150 m/z

Clonidine, acetyl derivative

VII-11-B-i

Cl N

C11H11Cl2N3O MW: 272.13

N

50

Cl

H 3COC

171.9

85.0

270.9

135.9

108.9

208.0

0 50

100

Relative Int. (%)

100

D N D D N D H 3COC

50

150

200

250

198.0

H

Cl

300

240.0

Clonidine-d4, acetyl derivative

VII-11-B-ii

N

C11H7D4Cl2N3O MW: 276.15

Cl

171.9

89.0

109.0

275.0

212.0

135.9

0 50

100

150

200

250

300


100

H 3COC

Cl

N

VII-11-C-i

236.0

194.0

278.0

Clonidine, di-acetyl derivative

N

C13H13Cl2N3O2 MW: 314.16

N

50

Cl

H 3COC

171.9

128.0

85.0

313.0

208.0


100

100 H 3COC D N D D N D H 3COC

50

89.1

150

200

250 240.0

198.0 Cl N

300

Clonidine-d4, di-acetyl derivative

282.0

VII-11-C-ii

350

C13H9D4Cl2N3O2 MW: 318.19

Cl

132.0

171.9

317.0

212.0

0 50

100

150

200 m/z



250

300

350

367


Relative Int. (%)

100

VII-11-D-i 50

N

73.0

Clonidine, trimethylsilyl derivative

Cl

C12H17Cl2N3Si MW: 302.27

N

N

142.0 99.0

Cl

266.0

H

(H3C)3Si

117.0

301.0

242.9

0 50

100

150

200

Relative Int. (%)

100

H D N D D N D (H3C)3Si

VII-11-D-ii 146.0

50 99.0

73.0

250

300

350

Cl

Clonidine-d4, trimethylsilyl derivative

Cl

C12H13D4Cl2N3Si MW: 306.29

270.0 N

305.0 242.9

123.9

0 50

Relative Int. (%)

100

100

150

Clonidine, di-trimethylsilyl derivative

200 m/z

N

300

350

338.1

(H3C)3Si

VII-11-E-i

C15H25Cl2N3Si2 MW: 374.45

50

250

Cl N

N

214.1

73.0

Cl

(H3C)3Si

322.0

172.1

358.0

373.1


100

100

150

Clonidine-d4, di-trimethylsilyl derivative

200

(H3C)3Si D N D D N D

VII-11-E-ii

C15H21D4Cl2N3Si2 MW: 378.48

50

250

218.1

(H3C)3Si

73.0

300

350

400

342.1 Cl

N Cl

362.1

326.1

176.1

377.1

0 50

100

150

200

250

300

350

400


100

252.1

(H3C)3C(H3C)2Si N

N

C21H37Cl2N3Si2 MW: 458.61

N

50

(H3C)3C(H3C)2Si

Cl

286.0

93.0

0 50

100

150

200

250


Clonidine, di-t-butyldimethylsilyl derivative

VII-11-F-i

Cl

256.1

(H3C)3C(H3C)2Si Cl D N D N D N D Cl (H3C)3C(H3C)2Si

50

300

150

290.0

200

250

300 m/z



400

450

500

Clonidine-d4, di-t-butyldimethylsilyl derivative C21H33D4Cl2N3Si2 MW: 462.63

93.0

100

350

VII-11-F-ii

0 50

343.1

347.1

350

400

450

500

368

Figure VII-12. Mass spectra of chloramphenicol and its deuterated analogs (chloramphenicol-d5): (A) underivatized; (B) [acetyl]2-derivatized; (C) TMS-derivatized; (D) [TMS]2-derivatized.

Relative Int. (%)

100

99.0

NO2

VII-12-A-i

50

Chloramphenicol (CAS NO.56-75-7) C11H12Cl2N2O5 MW: 323.13

HO CH

115.0

70.0

HC N COCHCl 2 H

162.0 207.0

179.0

HOH2C

0 50

100

Relative Int. (%)

100

150

99.0

200

250

VII-12-A-ii

NO2

D

300

Chloramphenicol-d5

D

C11H7D5Cl2N2O5 MW: 328.15

D D HO CD

50 70.0

HC

167.0

120.0

212.0

184.0

HOH2C

350

N COCHCl 2 H

0 50

Relative Int. (%)

100

100

43.0

150

VII-12-B-i

200 m/z

250

NO2

153.0

50

169.9

350

Chloramphenicol, di-acetyl derivative C15H16Cl2N2O7 MW: 407.20

H3COCO CH

213.9

HC

118.0

70.0

300

N COCHCl 2

HOH2C COCH 3

281.0


100

90 43.0

140

190

240

290

171.9

50

211.9

118.0

NO2

390

440

D

Chloramphenicol-d5, di-acetyl derivative

D D H3COCO CD

C15H11D5Cl2N2O7 MW: 412.23

D

158.0

VII-12-B-ii

70.0

340

HC N COCHCl 2 HOH2C COCH 3

286.0

0 40

Relative Int. (%)

100

90

140

190

240 m/z

73.0

290

340

NO2

224.0

390

Chloramphenicol, trimethylsilyl derivative

VII-12-C-i

C14H20Cl2N2O5Si MW: 395.31

HO CH

50 84.0

103.0

147.0

HC N COCHCl 2

252.0

215.1

440

HOH2C Si(CH3)3

321.0

351.1


100

100

150

200

250 229.0

73.0

VII-12-C-ii

50 84.0

103.0

147.0

257.0

215.0

300

350

400

D

Chloramphenicol-d5, trimethylsilyl derivative

D D HO CD

C14H15D5Cl2N2O5Si MW: 400.34

D

NO2

HC N COCHCl 2 Si(CH3)3

HOH2C

326.1

356.1

0 50

100

150

200

250 m/z



300

350

400

369


Relative Int. (%)

100

NO2

73.0

VII-12-D-i

314.0 297.1

50 147.0

C17H28Cl2N2O5Si2 MW: 467.49

(H3C)3SiO CH

224.0 98.0

Chloramphenicol, di-trimethylsilyl derivative

HC

244.0

HOH2C

N COCHCl 2 Si(CH3)3

455.1


100

100

150

200

250

300

350 314.0

73.0

VII-12-D-ii 229.0 98.0

147.0

NO2

D D (H3C)3SiO CD

C17H23D5Cl2N2O5Si2 MW: 472.52

HOH2C

N COCHCl 2 Si(CH3)3

460.2

0 50

100

150

200

250

300 m/z



500

Chloramphenicol-d5, di-trimethylsilyl derivative

HC

244.0

450

D

D

302.1

50

400

350

400

450

500

370

Figure VII-13. Mass spectra of melatonin and its deuterated analogs (melatonin-d7): (A) underivatized; (B) acetylderivatized; (C) TFA-derivatized; (D) PFP-derivatized; (E) HFB-derivatized; (F) TMS-derivatized. Relative Int. (%)

100

160.1

VII-13-A-i

50

173.1

Melatonin (CAS NO.73-31-4)

CH 2CH 2 O

H3CO

NH

N

C

C13H16N2O2 MW: 232.27

CH 3

H

145.0

117.1

80.1

232.1

0 50

100

150

Relative Int. (%)

100

200

250

162.1

VII-13-A-ii

50

Melatonin-d7

CD 2CD 2 O

H3CO

C

NH

N

176.1

C13H9D7N2O2 MW: 239.32

CD 3

H

119.1

80.1

147.0

239.1

0

Relative. Int. (%)

50

100

100

160.1

CH 2CH 2 O

H3CO

NH

N

50

150 m/z

C

200

173.1

Melatonin, acetyl derivative

VII-13-B-i

CH 3

C15H18N2O3 MW: 274.31

COCH 3

145.0

117.1

80.1

274.1 232.1

0 50 Relative. Int. (%)

250

100

150

100 NH

N

50

162.1

CD 2CD 2 O

H3CO

C

200 176.1

250

300 Melatonin-d7, acetyl derivative

VII-13-B-ii

CD 3

C15H11D7N2O3 MW: 281.35

COCH 3

147.1

119.1

80.1

281.1 239.1

0 50

100

150

200

250

300


100

CH 2CH 2 O

H3CO

NH

N

50

C

CH 3

269.0

VII-13-C-i

Melatonin, trifluoroacetyl derivative C15H15F3N2O3 MW: 328.29

COCF 3

72.1

159.1

144.0

116.1

256.0

328.1

0 50

100

150

Relative Int. (%)

100

CD 2CD 2 O

H3CO

NH

N

50

200

C

CD 3

250 272.1

VII-13-C-ii

300

Melatonin-d7, trifluoroacetyl derivative C15H8D7F3N2O3 MW: 335.32

COCF 3

161.1 69.0

118.0

350

258.0

146.1

335.1

0 50

100

150

200 m/z



250

300

350

371


Relative Int. (%)

100

319.0

Melatonin, pentafluoropropionyl derivative

CH 2CH 2 O

H3CO

C16H15F5N2O3 MW: 378.29

50

NH

N

C

VII-13-E-i

CH 3

COC 2 F 5

159.1

306.0

144.1

89.0

378.1


100

100

150

200

C

VII-13-E-ii

CD 3

308.0

146.0

100

400

COC 2 F 5

161.1

50

NH

N

91.0

350

CD 2CD 2 O

H3CO

C16H8D7F5N2O3 MW: 385.33

0

300 322.1

Melatonin-d7, pentafluoropropionyl derivative

50

250

385.1

150

200

250

300

350

400


100

Melatonin, heptafluorobutyryl derivative C17H15F7N2O3 MW: 428.30

50

369.0

CH 2CH 2 O

H3CO

NH

N

C

VII-13-F-i

CH 3

COC 3 F 7

159.1 144.1

69.0

356.0

428.1


100

100

150

200

Melatonin-d7, heptafluorobutyryl derivative

250

350

N

NH

C

VII-13-F-ii

CD 3

146.1

358.0

435.1

0 50

Relative Int. (%)

100

100

150

VII-13-G-i

250 m/z

NH

C

300

350

232.1

CH 2CH 2 O N

73.1

50

200

H3CO

450

COC 3 F 7

161.1 69.0

400 372.1

CD 2CD 2 O

H3CO

C17H8D7F7N2O3 MW: 435.34

50

300

245.1

400

450

Melatonin, trimethylsilyl derivative

CH 3

C16H24N2O2Si MW: 304.45

Si(CH3)3

304.1


100

100

VII-13-G-ii

200

250 234.1

CD 2CD 2 O

H3CO

NH

N

73.1

50

150

C

248.1

300

350

Melatonin-d7, trimethylsilyl derivative

CD 3

C16H17D7N2O2Si MW: 311.50

Si(CH3)3

310.1

0 50

100

150

200 m/z



250

300

350

373

PART THREE CROSS-CONTRIBUTIONS OF ION INTENSITY BETWEEN ANALYTES AND THEIR ISOTOPICALLY LABELED ANALOGS IN VARIOUS DERIVATIZATION FORMS

Table I — Stimulants


375

Appendix Two Cross-Contributions between Ions Designating Drugs and Their Isotopically Labeled Analogs in Various Derivatization Forms Table of Contents for Appendix Two Table I. Cross-contributions between ions designating drugs and their isotopically labeled analogs in various derivatization forms — Stimulants ........................................................................................................................................................................ 377 Table II. Cross-contributions between ions designating drugs and their isotopically labeled analogs in various derivatization forms — Opioids ............................................................................................................................................................................ 409 Table III. Cross-contributions between ions designating drugs and their isotopically labeled analogs in various derivatization forms — Hallucinogens .................................................................................................................................................................. 437 Table IV. Cross-contributions between ions designating drugs and their isotopically labeled analogs in various derivatization forms — Depressants/Hypnotics ..................................................................................................................................................... 449 Table V. Cross-contributions between ions designating drugs and their isotopically labeled analogs in various derivatization forms — Antianxiety Agents .......................................................................................................................................................... 459 Table VI. Cross-contributions between ions designating drugs and their isotopically labeled analogs in various derivatization forms — Antidepresants ................................................................................................................................................................. 477 Table VII. Cross-contributions between ions designating drugs and their isotopically labeled analogs in various derivatization forms — Others .............................................................................................................................................................................. 485



377

Summary of Drugs, Isotopic Analogs, and Chemical Derivatization Groups Included in Table I (Stimulants) Compound

Isotopic analog

Chemical derivatization group

Table #

Amphetamine

d5, d5 (ring), d6, d8, d10, d11

None, acetyl, TCA, TFA, PFP, HFB, 4-CB, PFB, propylformyl, l-TPC, d-TPC, l-MTPA, d-MTPA, TMS, t-BDMS, TFA/t-BDMS, PFP/t-BDMS, HFB/t-BDMS

I-1

Methamphetamine

d5, d8, d9, d11, d14

None, acetyl, TCA, TFA, PFP, HFB, 4-CB, PFB, propylformyl, l-TPC, d-TPC, l-MTPA, d-MTPA, TMS, t-BDMS

I-2

Ephedrine

d3

None, acetyl, TCA, [TFA]2, [PFP]2, [HFB]2, 4-CB, PFB, propylformyl, d-TPC, d-MTPA, [TMS]2

I-3

Phenylpropanolamine

d3

None, acetyl, TCA, [TFA]2, [PFP]2, [HFB]2, 4-CB, PFB, l-TPC, d-TPC, l-MTPA, d-MTPA, [TMS]2, t-BDMS, [t-BDMS]2, TFA/[t-BDMS]2, PFP/[t-BDMS]2, HFB/[t-BDMS]2

I-4

MDA

d5

None, acetyl, TCA, TFA, PFP, HFB, 4-CB, PFB, propylformyl, l-TPC, d-TPC, l-MTPA, d-MTPA, TMS, TFA/t-BDMS, PFP/t-BDMS, HFB/t-BDMS

I-5

MDMA

d5

None, acetyl, TCA, TFA, PFP, HFB, 4-CB, PFB, propylformyl, l-TPC, d-TPC, l-MTPA, d-MTPA, TMS

I-6

MDEA

d5, d6

None, acetyl, TCA, TFA, PFP, HFB, 4-CB, PFB, propylformyl, l-TPC, d-TPC, l-MTPA, d-MTPA, TMS

I-7

MBDB

d5

None, acetyl, TCA, TFA, PFP, HFB, 4-CB, PFB, propylformyl, l-TPC, d-TPC, l-MTPA d-MTPA, TMS

I-8

Selegiline

d8

None

I-9

N-Desmethylselegiline d11

None, acetyl, TCA, TFA, PFP, HFB, 4-CB, TMS

Fenfluramine

d10

None, acetyl, TCA, TFA, PFP, HFB, 4-CB

I-11

Norcocaine

d3

None, TFA, PFP, HFB, TMS

I-12

Cocaine

d3

None

I-13

Cocaethylene

d3, d8

None

I-14

Ecgonine methyl ester

d3

None, TFA, PFP, HFB, TMS, t-BDMS

I-15

Benzoylecgonine

d3, d8

Methyl, ethyl, propyl, butyl, PFPoxy, HFPoxy, TMS, t-BDMS

I-16

Ecgonine

d3

[TMS]2, [t-BDMS]2, HFPoxy/TFA, PFPoxy/PFP, HFPoxy/HFB

I-17

Anhydroecgonine methyl ester

d3

None

I-18

Caffeine

13C

None

I-19

Methylphenidate

d3

None, TFA, PFP, HFB, 4-CB, TMS

I-20

Ritalinic acid

d5

4-CB, [TMS]2, t-BDMS

I-21

3



I-10

379

Appendix Two — Table I Cross-Contributions Between ions Designating the Drugs and Their Isotopically Labeled Analogs in Various Derivatization Forms — Stimulants Table I-1a. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Amphetamine/amphetamine-d5 .................................................................................................................... 381 Table I-1b. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Amphetamine/amphetamine-d5 (ring) ......................................................................................................... 382 Table I-1c. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Amphetamine/amphetamine-d6 .................................................................................................................... 383 Table I-1d. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Amphetamine/amphetamine-d8 .................................................................................................................... 384 Table I-1e. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Amphetamine/amphetamine-d10 .................................................................................................................. 385 Table I-1f. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Amphetamine/amphetamine-d11 .................................................................................................................. 387 Table I-2a. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Methamphetamine/methamphetamine-d5 .................................................................................................... 388 Table I-2b. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Methamphetamine/methamphetamine-d8 .................................................................................................... 389 Table I-2c. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Methamphetamine/methamphetamine-d9 .................................................................................................... 390 Table I-2d. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Methamphetamine/methamphetamine-d11 ................................................................................................... 391 Table I-2e. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Methamphetamine/methamphetamine-d14 .................................................................................................. 392 Table I-3. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Ephedrine/ephedrine-d3 ............................................................................................................................... 393 Table I-4. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Phenylpropanolamine/phenylpropanolamine-d3 ......................................................................................... 394 Table I-5. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — MDA/MDA-d5 ............................................................................................................................................. 395 Table I-6. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — MDMA/MDMA-d5 ...................................................................................................................................... 396 Table I-7a. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — MDEA/MDEA-d5 ........................................................................................................................................ 397 Table I-7b. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — MDEA/MDEA-d6 ........................................................................................................................................ 398 Table I-8. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — MBDB/MBDB-d5 ........................................................................................................................................ 399 Table I-9. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Selegiline/selegiline-d8 ................................................................................................................................ 400 Table I-10. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — N-Desmethylselegiline/N-desmethylselegiline-d11 ..................................................................................... 401 Table I-11. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Fenfluramine/fenfluramine-d10 .................................................................................................................... 401 Table I-12. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Norcocaine/norcocaine-d3 ............................................................................................................................ 402 Table I — Stimulants


380

Table I-13. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Cocaine/cocaine-d3 ...................................................................................................................................... 402 Table I-14a. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Cocaethylene/cocaethylene-d3 ..................................................................................................................... 403 Table I-14b. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Cocaethylene/cocaethylene-d8 ..................................................................................................................... 403 Table I-15. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Ecgonine methyl ester/ecgonine methyl ester-d3 ......................................................................................... 403 Table I-16a. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Benzoylecgonine/benzoylecgonine-d3 ......................................................................................................... 404 Table I-16b. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Benzoylecgonine/benzoylecgonine-d8 ......................................................................................................... 404 Table I-17. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Ecgonine/ecgonine-d3 .................................................................................................................................. 405 Table I-18. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Anhydroecgonine methyl ester/anhydroecgonine methyl ester-d3 .............................................................. 406 Table I-19. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Caffeine/caffeine-13C3 .................................................................................................................................. 406 Table I-20. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Methylphenidate/methylphenidate-d3 .......................................................................................................... 406 Table I-21. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Ritalinic acid/ritalinic acid-d5 ......................................................................................................................................................................... 407

Appendix Two — Ion Intensity Cross-Contribution Data


381

Table I-1a. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Amphetamine/amphetamine-d5 CD Groupc

Amphetamine Ion (m/z)d Rel. int. Analog’s cont.

Amphetamine-d5 Ion (m/z)d Rel. int. Analog’s cont.

None

44

100

3.76

48

100

0.00

Acetyl

44 86

100 62.4

— 0.60

48 90

100 60.9

— 0.21

118 190

100 66.2

4.09 1.02

123 194

74.9 94.8

0.29 1.96

TCA TFA

140

100

0.23

144

100

0.85

PFP

118 190

73.0 100

3.48 0.10

123 194

44.3 100

0.19 0.14

HFB

118 223 240

57.3 3.35 100

3.77 0.69 0.09

123 227 244

33.9 5.11 100

0.38 0.50 0.01

4-CB

118 248 266 294

100 35.0 41.8 43.6

3.14 0.29 0.19 0.19

123 251 270 298

100 33.4 68.2 77.3

0.14 0.94 0.08 0.06

PFB

118 238

26.9 48.8

3.92 0.27

123 242

14.4 44.0

0.10 0.02

Propylformyl

130 162

100 3.40

0.03 0.27

134 167

100 3.31

0.96 0.27

l-TPC (l-l)

118 237

16.4 39.4

4.28 0.07

123 241

10.2 40.2

0.74 0.04

l-TPC (d-d)

118 237

17.3 40.3

4.10 0.07

123 241

10.2 42.6

0.68 0.04

l-MTPA (l-l)

91 162 260

65.8 14.7 55.7

— 2.51 1.70

93 167 264

33.2 16.7 55.5

— 2.45 0.11

l-MTPA (d-d)

91 162 260

71.9 17.3 57.9

— 2.75 1.92

93 167 264

37.1 19.5 56.2

— 4.90 0.11

TMS

116 192

100 7.80

0.54 1.85

120 197

100 7.77

0.73 0.20

t-BDMS

100 158 192 234

16.0 100 20.0 3.66

2.02 0.20 0.27 0.95

104 162 197 239

15.4 100 21.0 2.68

1.30 0.37 0.00 0.00

TFA/ t-BDMS

91 119 254 288 289

37.1 19.8 100 24.8 4.76

2.59 4.60 0.08 0.17 0.63

93 124 258 293 294

35.8 32.9 100 25.2 5.18

0.91 0.46 0.12 0.16 0.24

PFP/ t-BDMS

91 304 338 339

48.0 100 14.4 3.17

2.39 0.12 0.15 0.56

93 308 343 344

28.0 100 15.9 3.48

0.65 0.05 0.00 0.03

HFB/ t-BDMS

91 354 388 389

47.8 100 13.1 3.09

2.32 0.14 0.14 0.43

93 358 393 394

24.3 100 15.2 3.48

0.79 0.05 0.00 0.00

a

Relative intensities are based on full-scan data (see corresponding mass spectra in Appendix One), while cross-contributions (CC) are derived from selected ion monitoring (SIM) data. b Ion-pairs with 5% (or higher) CC by the analog are not listed. Table I — Stimulants


382

Table I-1a. (Continued) c d

See Table 2 in Chapter 2 for the abbreviations for the derivatization groups. The SIM intensities of the underlined ion-pair observed in two separate runs (for the analyte and its analog) were used to normalize the intensties of all ions for the calculations of CC data listed in the table.

Table I-1b. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Amphetamine/amphetamine-d5 (ring) CD Groupc



None

91

16.7

2.37

96

13.6

0.00

Acetyl

91 117 118

17.6 11.4 26.4

0.77 1.46 3.75

96 122 123

31.2 13.6 47.6

0.00 0.00 0.00

TCA

91 118

63.8 100

1.44 3.02

96 123

53.2 100

0.44 0.40

TFA

91 117 118

36.3 16.1 83.9

0.49 1.89 1.60

96 122 123

37.2 13.5 88.9

1.21 0.54 0.06

PFP

91 117 118

29.9 12.4 68.1

0.54 2.12 1.75

96 122 123

29.9 10.6 73.6

0.64 1.08 0.08

HFB

91 117 118

27.7 11.0 60.7

0.49 2.17 1.76

96 122 123

25.8 8.28 60.7

0.13 1.19 0.20

4-CB

91 118

49.9 100

0.54 1.36

96 123

43.3 100

0.45 0.17

PFB

91 118

11.3 26.9

1.02 2.42

96 123

10.4 27.9

0.16 0.05

Propylformyl

91

63.3

0.26

96

56.7

0.22

l-TPC (l-l)

91 117 118

21.8 3.87 16.4

— 3.26 3.40

96 122 123

29.6 3.35 15.1

— 1.99 0.45

l-TPC (d-d)

91 117 118

22.2 4.09 17.3

— 3.22 3.26

96 122 123

27.0 3.20 14.8

— 3.48 0.44

l-MTPA (l-l)

91 118 162

65.9 10.8 14.7

— 3.33 0.72

96 123 167

53.7 13.8 12.9

— 4.53 4.82

l-MTPA (d-d)

91

71.9

—

96

55.2

—

TMS

91 192

9.28 8.43

0.92 0.00

96 197

9.61 8.42

1.54 0.65

t-BDMS

91 192 234

7.29 20.0 3.66

1.03 0.35 0.70

96 197 239

8.35 19.4 3.50

2.93 0.13 0.25

TFA/ t-BDMS

91 288 289

37.1 24.8 4.76

0.41 0.11 0.28

96 293 294

66.2 21.7 4.46

0.35 0.02 0.19

PFP/ t-BDMS

91 338 339

48.0 14.4 3.17

0.38 0.06 0.62

96 343 344

43.9 14.3 3.13

0.85 0.01 0.02

HFB/ t-BDMS

91 388 389

47.8 13.1 3.09

0.54 0.04 0.65

96 393 394

43.6 12.3 3.03

0.09 0.00 0.00

a–d

See the corresponding footnotes in Table I-1a. Appendix Two — Ion Intensity Cross-Contribution Data


383

Table I-1c. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Amphetamine/amphetamine-d6 CD Groupc



None

44

100

3.50

48

100

2.28

Acetyl

44 86 118

100 62.4 45.4

0.96 0.68 2.08

48 90 123

100 58.5 43.9

0.69 1.00 0.13

TCA

91 118 190

63.8 100 66.2

4.47 1.65 0.55

93 123 194

59.2 100 72.4

1.45 0.30 3.15

TFA

140

100

0.26

144

100

0.87

PFP

91 118 190

36.0 73.0 100

4.69 2.42 0.09

93 123 194

30.4 69.8 100

2.47 0.12 0.19

HFB

91 118 223 240

27.0 57.3 3.35 100

4.27 2.46 0.57 0.06

93 123 227 244

33.7 76.4 5.52 100

3.28 0.23 0.64 0.01

4-CB

91 118 248 266 294

42.1 100 35.0 41.8 43.6

3.01 1.21 0.12 0.12 0.11

93 123 251 270 298

39.6 100 23.2 48.1 56.0

3.74 0.20 1.48 0.17 0.13

PFB

118 238

26.9 48.8

2.75 0.17

123 242

24.4 47.9

0.13 0.12

Propylformyl

91 130 162

41.7 100 3.40

3.78 0.00 0.10

93 134 168

37.1 100 3.50

1.20 1.00 0.02

l-TPC (l-l)

118 237

16.4 39.4

2.78 0.13

123 241

16.2 43.0

0.45 0.02

l-TPC (d-d)

118 237

17.3 40.3

2.69 0.14

123 241

17.1 44.0

0.39 0.01

l-MTPA (l-l)

91 162 234 260

65.8 14.7 15.3 55.7

— 0.21 2.12 0.23

93 168 236 264

57.0 17.7 9.78 53.9

— 0.84 1.54 0.18

l-MTPA (d-d)

91 162 234 260

71.9 17.3 16.1 57.9

— 0.32 3.12 0.30

93 168 236 264

56.2 19.1 10.3 58.6

— 1.91 1.59 0.18

TMS

116 192

100 7.80

0.30 1.74

120 198

100 7.82

0.47 1.04

t-BDMS

100 158 192 234

16.0 100 20.0 3.66

0.97 0.19 0.21 0.87

104 162 198 240

15.4 100 22.5 2.79

1.07 0.39 0.02 0.00

TFA/ t-BDMS

91 119 254 288 289

37.1 19.8 100 24.8 4.76

1.51 4.28 0.11 0.18 0.16

93 125 258 294 295

49.6 28.8 100 26.9 5.40

0.58 0.28 0.10 0.03 0.12

PFP/ t-BDMS

91 304 338 339

48.0 100 14.4 3.17

1.27 0.10 0.07 0.20

93 308 344 345

46.1 100 16.7 3.63

0.44 0.05 0.00 0.07



384

Table I-1c. (Continued) CD Groupc HFB/ t-BDMS

a–d

Amphetamine Ion (m/z)d Rel. int. Analog’s cont. 91 354 388 389

47.8 100 13.1 3.09

1.22 0.18 0.09 0.00

Amphetamine-d6 Ion (m/z)d Rel. int. Analog’s cont. 93 358 394 395

45.0 100 14.6 3.43

0.53 0.06 0.00 0.00

See the corresponding footnotes in Table I-1a.

Table I-1d. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Amphetamine/amphetamine-d8 CD Groupc



None

44 91

100 15.6

— 4.41

47 96

100 11.8

— 0.16

Acetyl

44 86 91 118

100 62.4 31.6 45.4

2.10 1.97 0.89 0.41

47 89 96 126

100 62.2 24.3 40.7

0.01 1.71 0.02 0.03

TCA

91 118 188 190

63.8 100 70.0 66.2

0.84 — 4.48 4.05

96 126 191 193

38.9 100 73.1 69.6

0.23 — 3.54 1.59

TFA

91 118 140

43.4 89.3 100

0.52 0.25 4.05

96 126 143

39.6 100 98.9

3.40 0.15 0.14

PFP

91 118 173 190

36.0 73.0 1.07 100

0.40 0.28 3.54 1.99

96 126 176 193

29.3 78.2 6.36 100

0.98 0.33 0.93 0.08

HFB

91 118 192 240

27.0 57.3 3.81 100

0.43 0.20 2.40 1.97

96 126 195 243

27.4 77.0 4.12 100

0.24 0.08 1.43 0.03

4-CB

91 118 220 248 266 294

42.1 100 12.4 35.0 41.8 43.6

0.32 0.16 2.37 1.96 1.75 1.78

96 126 223 250 269 297

26.8 100 7.25 19.4 41.1 46.5

0.57 0.05 2.44 2.19 0.55 0.15

PFB

91 118 238 239

11.3 26.9 48.8 5.04

0.32 1.51 1.89 4.58

96 126 241 242

10.8 25.5 47.7 5.27

0.05 0.07 0.06 1.08

Propylformyl

118 130 162

6.96 100 3.40

1.79 1.96 0.28

126 133 170

6.21 100 2.35

0.32 0.51 0.80

l-TPC (l-l)

237

39.4

1.84

240

43.0

0.10

l-TPC (d-d)

237

40.3

1.83

240

45.2

0.10

l-MTPA (l-l)

91 118 260

65.8 10.8 55.7

— 2.87 4.43

97 126 263

36.2 14.5 58.0

— 0.26 0.06



385

Table I-1d. (Continued) CD Groupc



l-MTPA (d-d)

91 118 260

71.9 12.1 57.9

— 3.00 4.88

97 126 263

39.9 15.3 57.9

— 0.21 0.06

TMS

91 116 192

11.5 100 7.80

1.71 2.18 2.05

96 119 200

9.97 100 6.64

2.37 0.74 2.58

t-BDMS

100 158 159 192 234

16.0 100 15.5 20.0 3.66

4.47 1.85 2.77 0.13 0.80

103 161 162 200 242

17.6 100 14.8 19.8 2.67

3.33 0.52 2.79 0.00 0.80

TFA/ t-BDMS

91 119 254 255 288 289

37.1 19.8 100 15.9 24.8 4.76

0.29 1.59 1.83 2.03 0.08 0.18

97 127 257 258 296 297

26.8 23.4 100 16.7 25.2 5.04

0.58 0.94 0.54 0.59 0.01 0.00

PFP/ t-BDMS

91 119 304 305 338 339

48.0 21.9 100 18.1 14.4 3.17

0.30 3.76 1.92 2.17 0.11 0.20

97 127 307 308 346 347

31.8 22.4 100 18.1 14.6 3.21

0.48 0.71 0.54 0.29 0.00 0.00

HFB/ t-BDMS

91 119 354 355 388 389

47.8 21.7 100 19.7 13.1 3.09

0.45 3.73 1.91 2.13 0.06 0.00

97 127 357 358 396 397

29.0 21.0 100 19.8 13.1 3.01

0.40 0.06 0.59 0.29 0.00 4.15

a–d


Table I-1e. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Amphetamine/amphetamine-d10 CD Groupc



None

44 91

100 15.6

1.60 0.14

48 97

100 11.5

0.38 0.65

Acetyl

44 86 118

100 62.4 45.4

0.81 0.54 0.21

48 90 127

100 61.0 27.1

0.06 0.73 0.17

TCA

91 92 118

63.8 8.81 100

1.13 2.53 0.40

97 98 128

63.1 37.4 89.5

3.89 3.43 1.35

TFA

91 118 140

43.4 89.3 100

0.30 0.17 0.44

97 128 144

37.7 51.8 100

3.14 1.02 0.85

PFP

91 118 190

36.0 73.0 100

0.21 0.20 0.08

97 128 194

32.7 47.9 100

0.23 1.03 0.22

HFB

91 118 223

27.0 57.3 3.35

0.27 0.09 0.49

97 128 227

31.3 47.3 7.98

0.17 0.72 0.43



386

Table I-1e. (Continued) CD Groupc



4-CB

91 118 248 266 294

42.1 100 35.0 41.8 43.6

0.45 0.19 0.27 0.18 0.15

97 128 251 270 298

52.8 100 33.3 69.2 82.9

0.16 0.42 1.01 0.06 0.04

PFB

91 118 238 239

11.3 26.9 48.8 5.04

0.32 1.42 0.15 2.01

97 128 242 243

11.3 15.0 48.8 4.98

0.02 0.11 0.04 0.17

Propylformyl

91 118 130 162

41.7 6.96 100 3.40

0.54 2.55 0.93 0.89

97 126 134 172

34.5 2.75 100 2.47

0.29 0.82 1.08 0.00

l-TPC (l-l)

237

39.4

0.05

241

44.9

0.05

l-TPC (d-d)

91 237

22.2 40.3

4.64 0.06

97 241

16.2 46.4

4.93 0.02

l-MTPA (l-l)

91 118 162 234 260 261

65.8 10.8 14.7 15.3 55.7 7.73

— 2.31 0.30 4.11 0.17 2.29

97 128 172 236 264 265

38.1 10.2 13.8 5.75 56.0 7.49

— 2.17 0.14 1.48 0.10 0.14

l-MTPA (d-d)

91 118 162 260 261

71.9 12.1 17.3 57.9 7.93

— 2.83 0.48 0.33 2.64

97 128 172 264 265

41.6 11.1 16.3 59.3 8.01

— 2.00 0.16 0.10 0.16

TMS

91 116 192

11.5 100 7.80

2.50 0.30 2.11

97 120 202

10.3 100 7.20

1.05 0.51 1.04

t-BDMS

91 100 158 159 192 234

7.29 16.0 100 15.5 20.0 3.66

3.40 1.72 0.03 1.40 0.40 0.46

97 104 162 163 202 244

6.19 18.2 100 14.6 20.9 2.48

1.35 0.95 0.40 0.63 0.00 0.00

TFA/ t-BDMS

91 119 254 255 288 289

37.1 19.8 100 15.9 24.8 4.76

0.28 0.81 0.06 1.06 0.09 0.18

97 129 258 259 298 299

31.3 25.6 100 16.8 25.9 5.07

0.55 0.34 0.10 0.31 0.00 0.00

PFP/ t-BDMS

91 119 304 305 338 349

48.0 21.9 100 18.1 14.4 3.17

0.28 2.81 0.05 1.13 0.06 0.25

98 129 308 309 348 349

36.4 26.9 100 18.5 15.4 3.37

0.25 0.36 0.05 0.08 0.02 0.00

HFB/ t-BDMS

91 119 354 355 388 389

47.8 21.7 100 19.7 13.1 3.09

0.50 4.12 0.07 1.86 0.00 0.00

98 129 358 359 398 399

39.0 28.8 100 18.4 12.9 3.01

0.29 0.94 0.05 0.09 0.38 1.15

a–d



387

Table I-1f. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Amphetamine/amphetamine-d11 CD Groupc



None

44 91 120

100 15.6 3.54

4.96 3.80 3.98

48 98 128

100 12.0 2.99

2.68 3.88 2.31

Acetyl

44 86 91 118

100 62.4 31.6 45.4

0.19 0.06 3.51 0.18

48 90 98 128

100 61.1 34.4 42.9

0.43 1.26 0.16 0.28

TCA

91 118 190

63.8 100 66.2

0.82 0.27 2.45

98 128 194

66.8 100 68.3

2.18 1.38 3.41

TFA

91 118 140

43.4 89.3 100

0.30 0.17 0.38

98 128 144

41.6 82.3 100

0.35 0.64 0.86

PFP

91 118 190

36.0 73.0 100

0.15 0.20 0.09

98 128 194

36.1 72.7 100

0.13 0.63 0.00

HFB

91 118 223 240

27.0 57.3 3.35 100

0.19 0.09 0.53 0.06

98 128 227 244

38.5 74.8 7.08 100

0.08 0.45 0.47 0.01

4-CB

91 118 248 266 294

42.1 100 35.0 41.8 43.6

0.28 0.12 0.13 0.12 0.11

98 128 251 270 298

46.3 100 21.9 46.3 56.6

0.10 0.46 1.53 0.15 0.12

PFB

118 238

26.9 48.8

1.42 0.18

128 242

24.4 29.9

0.10 0.09

Propylformyl

91 130 118 162

41.7 100 6.96 3.40

0.32 — 0.47 0.00

98 134 126 173

46.8 100 3.84 2.19

0.01 — 0.72 0.68

l-TPC (l-l)

237

39.4

0.04

241

45.0

0.03

l-TPC (d-d)

237

40.3

0.05

241

45.7

0.02

l-MTPA (l-l)

91 118 162 234 260 261

65.8 10.8 14.7 15.3 55.7 7.73

— 1.21 0.11 1.83 0.06 4.77

98 128 173 236 264 265

71.1 10.7 14.9 10.4 55.9 7.43

— 3.49 0.77 1.20 0.17 0.32

l-MTPA (d-d)

91 118 162 234 260

71.9 12.1 17.3 16.1 57.9

— 1.36 0.21 2.73 0.13

98 128 173 236 264

70.5 11.0 16.3 11.1 59.7

— 3.54 0.77 1.26 0.14

TMS

91 116 192

11.5 100 7.80

2.70 0.09 0.11

98 120 203

12.5 100 6.51

2.85 0.54 1.44

t-BDMS

100 158 159 192 234

16.0 100 15.5 20.0 3.66

0.58 0.21 4.77 0.29 0.76

104 162 163 203 245

19.0 100 14.4 21.5 2.73

0.84 0.40 0.56 0.00 1.51

TFA/ t-BDMS

91 119 254 255 288 289

37.1 19.8 100 15.9 24.8 4.76

0.24 0.70 0.04 4.04 0.19 0.34

98 130 258 259 299 300

56.1 25.9 100 16.9 26.5 5.18

0.12 0.47 0.09 0.32 0.00 0.57



388

Table I-1f. (Continued) CD Groupc



PFP/ t-BDMS

91 119 304 305 338 339

48.0 21.9 100 18.1 14.4 3.17

0.29 2.83 0.07 3.96 0.08 0.27

98 130 308 309 349 350

65.9 26.6 100 18.5 15.8 3.22

0.17 0.55 0.05 0.03 0.00 0.00

HFB/ t-BDMS

91 119 354 355 388 389

47.8 21.7 100 19.7 14.4 3.17

0.35 3.16 0.05 4.10 0.00 0.00

98 130 358 359 399 400

59.4 23.7 100 19.3 14.0 3.22

0.16 1.54 0.05 0.11 0.21 0.23

a–d


Table I-2a. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Methamphetamine/methamphetamine-d5 CD Groupc

Methamphetamine Ion (m/z)d Rel. int. Analog’s cont.

Methamphetamine-d5 Ion (m/z)d Rel. int. Analog’s cont.

None

58

100

3.40

62

100

0.60

Acetyl

58 100

100 76.1

0.54 0.25

62 104

100 73.7

0.18 0.39

TCA

204

95.6

0.07

208

95.5

3.52

TFA

110 154

24.5 100

0.63 0.14

113 158

23.6 100

0.49 0.57

PFP

160 204

28.7 100

0.49 0.05

163 208

26.7 100

0.12 0.03

HFB

210 254

29.7 100

0.50 0.04

213 258

26.7 100

0.05 0.01

4-CB

262 280 308 309

11.3 13.2 100 11.7

0.06 0.01 0.06 0.81

266 284 312 313

10.6 12.9 100 11.7

0.17 0.88 0.04 0.07

PFB

252 253

83.7 9.69

0.23 0.96

256 257

85.4 9.63

0.01 0.44

Propylformyl

58 102 144 176

41.7 30.5 100 3.92

0.95 0.50 0.04 0.00

62 106 148 181

43.4 30.3 100 4.07

0.39 0.39 1.29 0.13

l-TPC(l-l)

58 176 251

46.8 2.01 45.8

0.35 1.70 0.04

62 181 255

50.2 2.16 49.6

0.22 0.78 0.03

l-TPC(d-d)

58 176 251

45.1 1.84 45.3

0.42 1.75 0.06

62 181 255

48.7 2.04 48.2

0.19 0.65 0.03

l-MTPA(l-l)

176 200 274 275

4.58 7.02 57.1 8.50

1.48 1.52 3.18 2.75

181 204 278 279

4.30 4.68 54.2 8.00

0.22 0.61 0.01 0.11

l-MTPA(d-d)

176 200 274 275

4.16 7.26 60.8 8.59

2.31 4.31 0.78 0.34

181 204 278 279

4.20 5.20 61.2 9.32

0.34 0.12 0.01 0.11



389

Table I-2a. (Continued) CD Groupc



TMS

130 206

100 7.05

0.13 0.37

134 211

100 6.28

0.62 0.17

t-BDMS

172 206 248

100 16.2 2.58

0.26 0.32 0.00

176 211 253

100 14.1 3.06

1.20 1.42 0.00

a–d


Table I-2b. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Methamphetamine/methamphetamine-d8 CD Groupc



None

58 134

100 2.79

— 3.24

65 139

100 2.05

— 4.40

Acetyl

58 100

100 76.1

0.39 0.25

62 107

100 72.9

3.10 0.02

TCA

202 204 206

100 95.6 30.6

0.96 0.38 2.13

209 211 213

100 96.4 31.3

0.21 0.08 0.07

TFA

110 154

24.5 100

0.41 0.22

113 161

23.1 100

0.54 0.09

PFP

160 204

28.7 100

0.12 0.04

163 211

27.3 100

0.08 0.01

HFB

210 254

29.7 100

0.17 0.05

213 261

23.3 100

0.07 0.01

4-CB

262 280 308 309

11.3 13.2 100 11.7

0.05 0.09 0.07 0.00

268 287 315 316

7.56 11.4 100 11.6

0.21 0.00 0.01 0.02

PFB

252 253

83.7 9.69

0.21 0.93

259 260

84.2 9.68

0.01 0.43

Propylformyl

102 144 176

30.5 100 3.92

0.31 0.04 0.12

109 151 184

31.0 100 4.19

0.13 0.02 0.11

l-TPC (l-l)

58 176 251

46.8 2.01 45.8

0.29 1.66 0.04

65 184 258

53.6 2.25 50.6

4.61 0.30 0.56

l-TPC (d-d)

58 176 251

45.1 1.84 45.3

0.31 1.66 0.04

65 184 258

51.7 2.13 50.5

4.65 0.38 0.60

l-MTPA (l-l)

176 200 274 275

4.58 7.02 57.1 8.50

0.37 1.22 3.31 3.28

184 204 281 282

4.23 4.88 57.2 8.18

0.21 0.09 0.00 0.23

l-MTPA (d-d)

176 200 274 275

4.58 7.26 60.8 8.59

1.27 2.64 2.11 2.48

184 204 281 282

4.09 5.41 63.8 9.35

0.48 0.13 0.00 0.31

TMS

130 206

100 7.05

0.00 0.07

137 214

100 6.26

0.03 1.54



390

Table I-2b. (Continued) CD Groupc t-BDMS a–d

Methamphetamine Ion (m/z)d Rel. int. Analog’s cont. 172 206

100 16.2

0.83 0.96

Methamphetamine-d8 Ion (m/z)d Rel. int. Analog’s cont. 179 214

100 16.3

0.00 0.13


Table I-2c. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Methamphetamine/methamphetamine-d9 CD Groupc


None

58

100

—

Acetyl

58 100

100 76.1

TCA

91 202 204

TFA

Methamphetamine-d9 Ion (m/z)d Rel. int. Analog’s cont. 65

100

—

0.43 0.26

65 107

100 70.4

4.00 0.82

42.8 100 95.6

4.14 0.10 0.19

93 209 211

32.6 100 96.2

1.54 0.24 0.16

110 118 154

24.5 29.4 100

0.72 4.87 0.29

113 123 161

23.1 26.2 100

0.51 0.62 0.12

PFP

160 204

28.7 100

0.12 0.05

163 211

26.6 100

0.10 0.01

HFB

91 118 210 254

16.8 23.9 29.7 100

4.89 4.97 0.17 0.06

93 123 213 261

10.3 18.0 25.3 100

2.14 0.15 0.06 0.01

4-CB

91 118 262 280 308 309

19.5 14.8 11.3 13.2 100 11.7

2.47 3.89 0.06 0.09 0.08 0.14

93 123 268 287 315 316

16.4 11.6 7.63 12.1 100 11.7

0.77 0.04 0.17 0.09 0.07 0.09

PFB

252 253

83.7 9.69

0.15 0.74

259 260

82.4 9.12

0.08 0.52

Propylformyl

102 144 176

30.5 100 3.92

0.00 0.00 0.23

109 151 185

32.5 100 3.98

0.14 0.03 0.21

l-TPC (l-l)

58 176 251

46.8 2.01 45.8

0.34 1.74 0.04

65 185 258

51.3 2.30 50.6

4.56 1.25 0.57

l-TPC(d-d)

58 176 251

45.1 1.84 45.3

0.35 1.74 0.04

65 185 258

49.1 2.19 50.1

4.62 1.53 0.61

l-MTPA (l-l)

176 200 274 275

4.58 7.02 57.1 8.50

0.82 0.50 0.08 0.22

185 204 281 282

4.35 4.87 57.8 8.50

1.28 0.49 0.00 0.00

l-MTPA (d-d)

176 200 274 275

4.58 7.26 60.8 8.59

0.96 1.43 0.11 0.14

185 204 281 282

4.17 5.57 63.9 9.09

2.02 0.32 0.00 0.00

TMS

130 206

100 7.05

0.00 0.00

137 215

100 6.35

0.02 0.00



391

Table I-2c. (Continued) CD Groupc t-BDMS

a–d

Methamphetamine Ion (m/z)d Rel. int. Analog’s cont. 172 206 248

100 16.2 2.58

0.72 1.01 0.00

Methamphetamine-d9 Ion (m/z)d Rel. int. Analog’s cont. 179 215 257

100 17.9 2.09

0.17 0.34 4.82


Table I-2d. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Methamphetamine/methamphetamine-d11 CD Groupc



None

58 91 134

100 11.1 2.79

3.49 4.00 3.72

64 96 142

100 7.21 2.07

0.63 0.11 0.19

Acetyl

58 91 100 118

100 18.2 76.1 9.50

— 1.40 0.40 0.86

64 96 106 126

100 9.80 74.1 4.88

— 0.00 0.11 0.00

TCA

91 202 204 206

42.8 100 95.6 30.6

1.16 0.05 0.67 1.20

96 208 210 212

23.0 100 95.3 30.6

1.60 3.21 0.07 0.14

TFA

91 118 154

14.5 29.4 100

1.16 0.27 0.12

96 126 160

9.69 30.2 100

2.98 0.87 0.18

PFP

91 118 160 204

13.1 22.0 28.7 100

0.63 0.28 1.36 0.06

96 126 163 210

7.75 21.8 25.8 100

0.66 0.56 0.10 0.00

HFB

91 118 210 254

16.8 23.9 29.7 100

0.68 0.25 0.28 0.05

96 126 213 260

8.25 21.3 26.9 100

0.47 0.22 0.05 0.00

4-CB

91 118 262 280 308 309

19.5 14.8 11.3 13.2 100 11.7

0.53 0.25 0.08 0.01 0.07 0.53

97 126 267 286 314 315

10.4 16.3 7.80 11.9 100 11.6

0.42 0.23 0.20 0.24 0.01 0.47

PFB

91 118 252 253

7.97 6.62 83.7 9.69

0.73 4.45 0.25 0.97

96 126 258 259

6.85 6.18 83.1 9.80

0.28 0.49 0.02 0.89

Propylformyl

58 91 102 144

41.7 26.2 30.5 100

1.37 1.83 0.51 0.10

64 96 108 150

45.9 16.0 30.5 100

0.60 0.20 0.59 0.13

l-TPC (l-l)

58 119 251

46.8 7.35 45.8

0.38 2.49 0.04

65 127 257

50.3 8.76 50.8

0.44 1.92 2.96

l-TPC (d-d)

58 119 251

45.1 7.59 45.3

0.39 2.35 0.04

65 127 257

47.3 9.09 52.0

0.45 1.93 3.13



392

Table I-2d. (Continued) CD Groupc



l-MTPA (l-l)

176 200 274 275

4.58 7.02 57.1 8.50

0.49 1.19 0.31 0.11

187 203 280 281

3.71 6.65 57.2 8.86

4.68 1.05 0.02 0.00

l-MTPA (d-d)

176 200 274 275

4.58 7.26 60.8 8.59

0.84 2.07 0.43 0.16

187 203 280 281

3.77 7.54 61.5 9.64

1.34 2.03 0.01 0.00

TMS

91 130 206

8.68 100 7.05

2.32 0.00 0.00

96 136 217

6.79 100 7.03

0.44 0.09 0.15

t-BDMS

172 206

100 16.2

1.37 2.71

178 217

100 18.2

0.24 0.00

a–d


Table I-2e. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Methamphetamine/methamphetamine-d14 CD Groupc



None

58 91 134

100 11.1 2.79

— 0.97 1.25

65 98 145

100 8.75 2.17

— 1.87 3.23

Acetyl

58 91 100 118

100 18.2 76.1 9.50

0.28 0.80 0.37 0.07

65 98 107 128

100 16.9 70.7 7.93

3.29 0.18 0.11 0.63

TCA

91 202 204

42.8 100 95.6

0.47 0.24 0.08

98 209 211

41.9 100 95.6

0.05 0.30 0.02

TFA

91 118 154

14.5 29.4 100

1.60 0.23 0.28

98 128 161

13.6 25.7 100

1.99 3.31 0.12

PFP

91 118 160 204

13.1 22.0 28.7 100

0.32 0.21 0.56 0.13

98 128 163 211

12.8 20.2 26.7 100

0.71 2.56 0.11 0.00

HFB

91 118 210 254

16.8 23.9 29.7 100

0.29 0.15 0.16 0.03

98 128 213 261

13.7 17.5 24.8 100

0.33 2.34 0.06 0.00

4-CB

91 118 262 280 308 309

19.5 14.8 11.3 13.2 100 11.7

0.36 0.17 0.10 0.09 0.08 0.00

98 128 268 287 315 316

19.7 11.7 7.63 12.2 100 12.0

0.16 0.64 0.16 0.04 0.02 0.00

PFB

91 118 252 253

7.97 6.62 83.7 9.69

0.24 4.50 0.02 0.58

98 128 259 260

8.98 5.27 80.6 9.17

0.08 0.72 0.03 0.44



393

Table I-2e. (Continued) CD Groupc



Propylformyl

91 102 144 176

26.2 30.5 100 3.92

1.52 0.23 0.41 0.45

98 109 151 190

30.9 32.5 100 3.09

0.12 0.18 0.03 2.71

l-TPC (l-l)

58 119 251

46.8 7.35 45.8

0.46 4.51 0.02

65 130 258

48.9 8.23 53.2

4.81 1.81 0.56

l-TPC (d-d)

58 119 251

45.1 7.59 45.3

0.46 4.73 0.02

65 130 258

48.3 8.44 51.0

4.74 1.72 0.58

l-MTPA (l-l)

200 274 275

7.02 57.1 8.50

0.57 0.02 0.07

204 281 282

5.11 59.9 8.82

0.90 0.00 0.00

l-MTPA (d-d)

200 274 275

7.26 60.8 8.59

0.46 0.25 0.31

204 281 282

5.15 64.1 9.78

0.24 0.00 0.00

TMS

91 130

8.68 100

1.89 0.50

98 137

9.26 100

0.82 0.02

t-BDMS

172 206

100 16.2

0.64 1.27

179 220

100 18.3

0.00 0.00

a–d


Table I-3. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Ephedrine/ephedrine-d3 CD Groupc

Ephedrine Ion (m/z)d Rel. int. Analog’s cont.

Ephedrine-d3 Ion (m/z)d Rel. int. Analog’s cont.

None

58

100

2.49

61

100

0.05

Acetyl

58 100 101 189

100 69.4 27.0 2.07

2.22 0.60 1.14 2.05

61 103 104 192

100 65.8 26.3 2.18

0.18 1.38 1.80 2.98

TCA

42 202 204

10.2 100 95.9

1.52 0.74 3.37

45 205 207

9.69 100 95.2

3.18 2.14 0.20

[TFA]2

110 154 244

20.0 100 3.34

0.55 0.06 2.86

113 157 247

19.4 100 4.15

0.42 0.11 0.17

[PFP]2

160 204 294

21.8 100 3.72

0.57 0.22 2.59

163 207 297

20.8 100 4.84

0.23 0.17 0.21

[HFB]2

210 254 344

19.4 100 5.40

0.50 0.30 2.10

213 257 347

22.6 100 3.81

0.41 0.46 0.43

4-CB

166 262 280 308 309

9.88 18.0 21.1 100 79.2

3.64 1.22 1.35 1.16 1.50

169 265 283 311 312

10.3 17.2 20.3 100 78.9

2.58 2.35 0.36 1.07 0.42

PFB

252 253

90.8 10.9

0.41 4.10

255 256

94.8 11.3

0.11 0.26



394

Table I-3. (Continued) CD Groupc

Ephedrine Ion (m/z)d Rel. int. Analog’s cont.

Ephedrine-d3 Ion (m/z)d Rel. int. Analog’s cont.

Propylformyl

58 144

50.9 100

2.31 0.08

61 147

50.1 100

0.20 0.50

l-TPC (d-d)

58 251

20.1 13.9

1.45 1.05

61 254

31.4 22.6

0.00 0.00

l-MTPA (d-d)

200 274 275

6.96 52.9 16.4

2.26 1.34 1.64

203 277 278

6.90 52.7 16.5

0.16 0.23 0.07

[TMS]2

130 294

100 2.31

0.31 0.72

133 297

100 2.29

1.55 1.68

a–d


Table I-4. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Phenylpropanolamine/phenylpropanolamine-d3 CD Groupc

Phenylpropanolamine Ion (m/z)d Rel. int. Analog’s cont.

Phenylpropanolamine-d3 Ion (m/z)d Rel. int. Analog’s cont.

None

44

100

2.76

47

100

0.01

Acetyl

86 176

100 6.35

0.36 4.69

89 179

93.1 5.42

3.83 0.68

TCA

160 188 190

18.0 100 94.8

3.63 1.64 2.22

163 191 193

18.6 100 95.0

3.67 4.86 1.71

[TFA]2

140

100

3.42

143

100

0.01

[PFP]2

190 280

100 17.6

1.66 4.97

193 283

100 43.4

0.12 0.11

[HFB]2

240

100

1.76

243

100

0.05

4-CB

248 266 294 295 338 384

19.3 30.6 100 11.0 6.09 15.8

0.28 0.23 0.31 3.40 0.40 0.33

250 269 297 298 341 387

9.57 27.8 100 10.7 6.22 15.4

4.43 0.18 0.09 0.09 1.97 0.21

PFB

238 239

69.3 7.32

0.40 2.17

241 242

69.7 7.53

0.13 0.00

l-TPC (l-l)

220 237

5.97 25.4

3.91 3.80

223 240

5.69 23.8

0.00 0.13

l-MTPA (l-l)

229 260 261

17.6 20.4 56.6

1.10 0.88 1.00

232 263 264

16.6 19.6 55.5

0.74 3.53 0.25

l-MTPA (d-d)

229 260 261

19.2 20.2 58.6

1.40 0.83 0.93

232 263 264

17.5 19.0 56.6

0.73 3.50 0.17

[TMS]2

116

100

3.71

119

100

1.01

t-BDMS

158

100

4.24

161

100

0.71

[t-BDMS]2

None (No ion pair meets the selection criteria)



395


Phenylpropanolamine Ion (m/z)d Rel. int. Analog’s cont.

Phenylpropanolamine-d3 Ion (m/z)d Rel. int. Analog’s cont.

TFA/ [t-BDMS]2

191 254 418 419

7.33 5.50 35.8 11.7

4.14 1.75 0.24 0.45

194 257 421 422

6.35 5.68 41.9 13.6

1.90 0.84 2.35 1.30

PFP/ [t-BDMS]2

304 468 469

6.07 36.9 12.2

1.39 0.25 0.96

307 471 472

6.14 33.5 10.5

1.16 2.51 1.40

HFB/ [t-BDMS]2

191 354 518 519

4.41 6.99 19.6 6.60

4.68 1.51 0.25 0.53

194 357 521 522

4.33 7.41 25.0 8.67

4.18 3.78 2.50 1.35

a–d


Table I-5. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — MDA/MDA-d5 CD Groupc

MDA Ion (m/z)d Rel. int.

Analog’s cont.

None

44

100

—

Acetyl

44 86 162 221

56.6 12.4 100 6.31

TCA

162 190 323

TFA

MDA-d5 Ion (m/z)d Rel. int.

Analog’s cont.

48

100

—

2.71 2.82 2.98 4.02

48 90 166 226

95.6 17.2 95.6 11.9

0.01 1.86 0.02 0.24

100 13.5 4.21

1.06 1.75 1.25

167 194 328

68.6 16.2 6.03

0.07 2.07 2.39

135 162 275

100 45.6 15.7

— 0.47 0.26

136 167 280

100 27.5 16.9

— 0.03 0.00

PFP

135 162 190 325

100 48.7 8.11 12.7

— 0.46 0.64 0.25

136 167 194 330

100 29.6 8.75 13.8

— 0.04 0.24 0.00

HFB

135 162 240 375

100 54.6 9.69 12.8

— 0.45 0.65 0.25

136 167 244 380

100 33.5 10.7 13.8

— 0.09 0.03 0.00

4-CB

162 248 266 429

100 8.86 9.08 4.99

1.30 2.35 2.64 1.23

166 251 270 434

74.4 7.37 12.6 7.79

0.09 0.57 0.05 0.00

PFB

162 238 373

77.6 16.5 4.82

0.78 1.44 2.86

166 232 378

35.9 15.9 5.96

0.09 0.12 0.00

Propylformyl

130 162 206 265

100 37.8 8.21 25.5

0.34 0.70 0.52 0.40

134 167 211 270

100 24.3 9.69 28.6

2.04 1.28 0.10 0.00

l-TPC (l-l)

135 237 372

19.2 7.51 7.65

— 0.51 0.35

136 241 377

12.1 4.73 5.31

— 0.10 0.02



396


MDA Ion (m/z)d Rel. int.

Analog’s cont.

MDA-d5 Ion (m/z)d Rel. int.

Analog’s cont.

l-TPC (d-d)

135 237 372

19.1 8.92 6.77

— 0.53 0.33

136 241 377

11.7 5.67 5.27

— 0.00 0.07

l-MTPA (l-l)

162 163 206 228 260

100 22.6 5.03 3.66 5.38

0.20 4.98 0.85 0.57 0.15

166 167 211 232 264

74.8 86.9 8.04 3.18 7.29

0.07 0.30 0.59 0.87 0.21

l-MTPA (d-d)

162 163 206 228 260

100 24.0 6.00 3.82 5.48

0.23 4.51 0.83 0.63 0.23

166 167 211 232 264

76.5 88.4 9.21 3.14 6.87

0.06 0.34 0.33 0.93 0.30

TMS

116 236

100 6.22

0.21 0.85

120 241

100 3.53

0.22 0.11

t-BDMS

100 158 236 278

6.60 100 3.98 2.10

2.89 0.04 0.49 0.13

104 162 241 286

5.80 100 4.40 2.00

7.35 0.52 0.08 0.26

TFA/ t-BDMS

163 254 332 389

20.5 100 8.12 12.1

1.61 0.04 0.98 0.11

168 258 337 394

20.7 100 9.36 14.0

0.24 0.23 0.20 0.03

PFP/ t-BDMS

163 304 382 439

12.4 100 9.50 14.9

0.75 0.03 0.69 2.75

168 308 387 444

18.1 100 10.7 13.6

0.56 0.50 0.36 0.20

HFB/ t-BDMS

163 354 432 489

16.3 100 8.44 10.6

0.73 0.03 0.24 0.12

168 358 437 494

25.0 100 7.97 8.32

0.12 0.17 0.30 0.45

a–d


Table I-6. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — MDMA/MDMA-d5 CD Groupc

MDMA Ion (m/z)d Rel. int.

Analog’s cont.

MDMA-d5 Ion (m/z)d Rel. int.

Analog’s cont.

None

58

100

2.38

62

100

0.67

Acetyl

58 162 235

100 89.3 2.70

1.20 2.37 1.77

62 164 240

100 46.1 2.32

0.35 2.24 0.00

TCA

162 204

100 82.0

1.43 0.14

164 208

66.4 94.7

3.79 3.60

TFA

110 154 289

29.7 100 14.0

0.37 0.04 0.04

113 158 294

30.0 100 15.1

0.08 0.02 0.00

PFP

204 339

100 9.81

0.02 0.09

208 344

100 10.1

0.02 0.00

HFB

162 210 254 389

71.7 37.8 100 7.35

1.56 0.60 0.03 0.05

164 213 258 394

39.7 36.5 100 7.32

3.44 0.02 0.00 0.00



397


MDMA Ion (m/z)d Rel. int.

Analog’s cont.

MDMA-d5 Ion (m/z)d Rel. int.

Analog’s cont.

4-CB

162 262 280 308 443

100 17.0 19.6 66.6 2.04

1.91 0.17 0.14 0.11 0.11

164 266 284 312 448

84.6 24.9 29.0 100 3.18

2.97 0.14 0.05 0.01 0.00

PFB

162 252 253 387

43.2 39.7 4.62 1.36

2.64 0.57 2.36 3.96

164 256 257 392

23.6 40.4 4.62 1.51

1.27 0.02 0.24 0.00

Propylformyl

58 102 144 220 279

38.2 35.5 100 4.71 7.82

0.68 0.36 0.02 3.73 0.32

62 106 148 225 284

41.5 41.5 100 4.91 6.78

0.57 3.10 0.92 0.25 0.32

l-TPC (l-l)

58 251 386

39.0 12.7 2.71

0.30 0.08 0.04

62 255 391

40.0 13.0 3.37

0.35 0.07 0.03

l-TPC (d-d)

58 251 386

30.8 11.4 3.42

0.33 0.06 0.05

62 255 391

38.6 9.86 2.44

0.43 0.06 0.08

l-MTPA (l-l)

162 200 274

53.4 5.91 16.7

1.95 0.86 0.38

164 204 278

31.4 4.31 18.6

2.05 0.58 0.05

l-MTPA (d-d)

162 200 274

52.4 5.90 16.7

2.07 0.94 0.43

164 204 278

30.7 4.44 17.7

2.10 0.71 0.05

TMS

130 250

100 3.90

0.11 1.26

134 255

100 5.98

0.40 0.23

t-BDMS

172 173

100 15.8

0.01 0.43

176 177

100 16.0

0.30 1.30

a–d


Table I-7a. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — MDEA/MDEA-d5 CD Groupc

MDEA Ion (m/z)d Rel. int.

Analog’s cont.

MDEA-d5 Ion (m/z)d Rel. int.

Analog’s cont.

None

72

100

1.22

77

100

7.21

Acetyl

72 114

100 28.4

— 0.54

77 119

100 29.5

— 0.90

TCA

216 218

100 93.3

0.10 0.10

221 223

100 93.0

2.04 0.30

TFA

168 303

100 8.26

0.02 0.02

173 308

100 9.29

0.14 0.00

PFP

218 353

100 6.16

0.01 0.06

223 358

100 6.00

0.05 0.00

HFB

268 403

100 4.92

0.03 0.14

273 408

100 4.54

0.07 1.33

4-CB

276 294 322 323

10.7 13.0 81.6 10.8

0.21 0.17 0.04 0.18

281 299 327 328

11.7 15.1 100 13.1

0.55 0.12 0.03 0.08



398

Table I-7a. (Continued) CD Groupc


Analog’s cont.


Analog’s cont.

PFB

266 267

46.8 6.59

0.07 1.54

271 272

46.0 5.63

0.23 1.55

Propylformyl

158 116 234 293

100 32.0 2.55 3.42

— 0.36 0.17 0.04

163 121 239 298

100 31.9 3.00 3.45

— 1.80 0.35 0.07

l-TPC (l-l)

72 265 400

60.1 14.9 1.22

— 0.05 0.00

77 270 405

56.1 18.4 2.03

— 0.05 0.00

l-TPC (d-d)

72 265 400

54.0 12.8 1.57

— 0.08 0.00

77 270 405

50.1 15.5 2.57

— 0.07 0.05

l-MTPA (l-l)

214 262 288 289

6.84 2.52 27.5 4.31

0.34 4.45 0.18 0.27

219 267 293 294

6.59 2.52 26.7 4.16

0.34 0.00 0.07 0.28

l-MTPA (d-d)

214 288 289

6.51 27.7 4.26

0.48 0.23 0.29

219 293 294

6.72 26.6 4.27

0.34 0.12 0.35

TMS

144 264

100 5.92

0.06 0.26

149 269

100 7.09

0.70 0.13

a–d


Table I-7b. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — MDEA/MDEA-d6 CD Groupc


Analog’s cont.


Analog’s cont.

None

72

100

1.00

78

100

1.67

Acetyl

72 114 162

100 28.4 57.1

0.72 0.63 1.64

78 120 165

100 29.2 75.1

2.00 0.59 0.16

TCA

162 216 218 220 351

75.7 100 93.3 2.28 2.64

1.24 0.09 0.11 1.31 0.04

165 222 224 226 357

78.6 100 92.6 30.4 3.12

0.34 3.28 0.06 0.10 3.89

TFA

140 162 168 303

36.2 63.0 100 8.26

0.25 1.09 0.10 0.01

144 165 174 309

26.4 68.5 100 9.36

0.39 0.12 0.19 0.00

PFP

162 190 218 353

58.6 41.1 100 6.16

0.75 0.29 0.06 0.00

165 194 224 359

63.1 29.1 100 5.73

0.23 0.05 0.01 0.00

HFB

162 240 268 403

55.5 43.0 100 4.92

1.26 0.67 0.04 0.05

165 244 274 409

59.8 29.5 100 4.38

0.17 0.02 0.01 0.00



399

Table I-7b. (Continued) CD Groupc


Analog’s cont.


Analog’s cont.

4-CB

162 163 276 294 322 323

100 31.2 10.7 13.0 81.6 10.8

0.95 3.01 0.09 0.11 0.04 0.10

165 166 281 300 328 329

100 31.3 8.28 11.1 82.9 10.8

0.27 0.45 0.61 0.09 0.01 0.05

PFB

162 266 267

39.3 46.8 6.59

1.02 0.43 0.00

165 272 273

40.7 50.3 6.48

0.18 0.07 0.42

Propylformyl

72 116 158 234 293

40.7 32.0 100 2.55 3.42

0.15 0.20 0.01 0.11 0.02

78 122 164 240 299

41.5 33.4 100 2.78 3.37

4.59 1.19 0.92 0.19 0.06

l-TPC (l-l)

72 162 265

60.1 65.8 14.9

0.56 0.94 0.16

78 165 271

49.3 59.3 13.6

3.72 1.23 0.24

l-TPC (d-d)

72 162 265

54.0 85.3 12.8

0.62 0.90 0.11

78 165 271

41.6 75.3 11.7

4.16 0.99 0.26

l-MTPA (l-l)

162 163 214 288 289

44.5 11.2 6.48 27.5 4.31

0.68 2.39 0.49 0.14 0.21

165 166 217 294 295

45.1 11.2 6.56 25.8 4.18

0.26 0.24 0.10 0.07 0.00

l-MTPA (d-d)

162 163 214 288 289

41.8 10.0 6.51 27.7 4.26

1.06 3.07 0.48 0.24 0.35

165 166 217 294 295

42.7 10.3 6.58 26.2 4.18

0.31 0.30 0.18 0.08 0.00

TMS

144 264

100 5.92

0.07 0.23

150 270

100 6.75

0.17 0.20

a–d


Table I-8. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — MBDB/MBDB-d5 CD Groupc

MBDB Ion (m/z)d Rel. int.

Analog’s cont.

MBDB-d5 Ion (m/z)d Rel. int.

Analog’s cont.

None

72

100

4.43

76

100

0.66

Acetyl

72 114 249

100 34.6 1.27

0.70 0.59 0.98

76 118 254

100 32.3 1.24

0.61 3.39 0.71

TCA

176 218 351

100 91.4 3.74

1.83 0.32 0.33

178 222 356

61.5 93.8 4.25

1.72 2.13 2.89



400


MBDB Ion (m/z)d Rel. int.

Analog’s cont.

MBDB-d5 Ion (m/z)d Rel. int.

Analog’s cont.

TFA

110 168 303

18.2 100 11.6

0.37 0.03 0.02

113 172 308

18.1 100 12.1

0.45 0.07 0.00

PFP

160 176 190 218 353

28.3 67.8 5.25 100 7.75

0.43 1.03 1.87 0.02 0.04

163 178 194 222 358

28.2 37.5 3.29 100 8.10

0.65 4.02 0.66 0.03 0.10

HFB

176 210 268 403

61.9 27.6 100 5.86

0.95 1.63 0.02 0.03

178 213 272 408

34.1 26.2 100 6.00

3.21 0.20 0.03 0.00

4-CB

176 276 294 322 457

100 28.4 24.5 75.3 2.35

1.97 0.13 0.32 0.09 0.30

178 280 298 326 462

71.2 33.8 30.9 100 3.43

2.15 0.19 0.03 0.02 0.00

PFB

176 266

46.0 51.8

2.56 0.45

178 270

25.4 53.2

3.57 0.08

Propylformyl

72 116 158 234 293

42.1 44.5 100 3.15 4.26

0.30 0.85 0.00 0.75 0.02

76 120 162 239 298

39.2 43.3 100 3.82 5.36

1.49 0.89 0.31 0.03 0.00

l-TPC (l-l)

72 265 400

58.3 16.3 3.21

0.37 0.00 0.00

76 269 405

63.2 16.3 3.27

0.59 0.02 0.00

l-TPC (d-d)

72 265 400

52.2 12.5 2.54

0.43 0.00 0.00

76 269 405

52.2 13.3 3.04

0.63 0.03 0.10

l-MTPA (l-l)

176 248 288

55.8 4.41 20.2

2.36 2.84 1.05

178 252 292

30.4 2.62 20.4

1.47 0.29 0.07

l-MTPA (d-d)

176 248 288

55.3 4.35 20.8

2.51 4.08 1.25

178 252 292

31.2 2.60 21.1

1.43 0.33 0.07

TMS

144 250 264

100 2.14 4.53

0.08 1.22 0.29

148 255 269

100 2.07 4.42

0.65 0.00 0.10

a–d


Table I-9. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Selegiline/selegiline-d8 CD Groupc None a–d

Selegiline Ion (m/z)d Rel. int. 96

100

Analog’s cont. 0.49

Selegiline-d8 Ion (m/z)d Rel. int. 103

100




Analog’s cont. 1.03

401

Table I-10. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — N-Desmethylselegiline/N-desmethylselegiline-d11 CD Groupc

N-Desmethylselegiline Ion (m/z)d Rel. int. Analog’s cont.

N-Desmethylselegiline-d11 Ion (m/z)d Rel. int. Analog’s cont.

None

82 91

100 16.3

3.61 0.73

86 98

100 15.0

0.14 0.30

Acetyl

82 91 124

100 16.9 44.6

2.21 1.60 1.25

86 98 128

100 18.7 48.9

0.30 2.69 1.53

TCA

91 228

49.8 96.0

1.25 0.79

98 232

51.7 95.5

0.05 3.55

TFA

91 118 178

24.2 41.1 100

0.50 0.47 0.16

98 128 182

24.8 36.8 100

0.32 2.90 0.04

PFP

91 118 228

29.3 37.9 100

1.43 1.50 1.15

98 128 232

26.5 29.2 100

0.20 4.83 0.00

HFB

91 118 278

27.3 35.4 100

1.39 2.75 1.20

98 128 282

32.6 32.6 100

0.11 2.79 1.04

4-CB

91 118 304 332

55.0 43.9 4.90 100

0.99 1.85 0.76 0.19

98 128 308 336

54.5 31.9 4.67 100

0.00 3.01 2.64 0.06

TMS

91 154 230

11.4 100 3.02

1.64 0.99 1.99

98 158 241

12.8 100 3.53

1.40 0.01 0.79

a–d


Table I-11. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Fenfluramine/fenfluramine-d10 CD Groupc

Fenfluramine Ion (m/z)d Rel. int. Analog’s cont.

Fenfluramine-d10 Ion (m/z)d Rel. int. Analog’s cont.

None

72 73 230

100 6.51 2.73

0.58 3.96 1.66

81 82 239

100 7.32 1.10

0.73 3.84 3.14

Acetyl

72 114 216 254

100 58.8 3.35 2.39

0.13 0.69 0.36 0.29

81 123 223 264

100 55.1 2.53 2.56

0.08 0.10 0.00 0.00

TCA

159 216 218 220

58.0 100 95.4 30.7

2.70 0.25 0.29 1.29

161 225 227 229

32.5 100 94.6 30.6

0.53 0.01 0.07 0.84

TFA

159 168 186 308

13.5 100 4.60 4.48

2.68 0.61 2.61 0.00

161 177 191 318

4.91 100 2.27 4.21

2.73 0.10 1.98 0.00

PFP

159 218 358

13.7 100 4.02

2.25 0.11 0.11

161 227 368

5.66 100 3.82

2.72 1.54 1.22



402


Fenfluramine Ion (m/z)d Rel. int. Analog’s cont.

Fenfluramine-d10 Ion (m/z)d Rel. int. Analog’s cont.

HFB

159 240 268 269 408

15.4 26.3 100 9.04 3.39

2.94 0.74 0.13 0.38 0.00

161 245 277 278 418

6.66 22.2 100 8.92 3.32

1.19 0.03 0.00 0.06 0.00

4-CB

159 220 276 294 322

39.5 8.98 8.12 9.55 100

3.83 2.45 0.47 0.57 0.29

161 224 284 303 331

20.5 9.44 5.48 7.79 100

0.84 3.26 0.89 0.23 0.00

a–d


Table I-12. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Norcocaine/norcocaine-d3 CD Groupc

Norcocaine Ion (m/z)d Rel. int. Analog’s cont.

Norcocaine-d3 Ion (m/z)d Rel. int. Analog’s cont.

None

168 289

100 11.0

1.18 0.85

171 292

100 10.6

0.16 0.26

TFA

100 194 263 280 316 385

32.5 30.5 38.1 5.00 3.47 2.43

1.44 0.58 0.09 0.14 0.07 0.00

103 197 266 283 319 388

34.1 32.0 39.7 5.26 3.61 2.67

1.19 0.35 0.18 0.37 0.34 0.38

PFP

100 194 435

32.1 30.8 2.77

3.25 1.22 0.97

103 197 438

33.9 31.8 2.81

1.18 0.23 0.41

HFB

194 334 363 380 485

27.8 9.10 43.0 4.28 2.98

0.45 2.25 0.07 0.53 0.05

197 337 366 383 488

26.5 7.38 37.2 3.91 2.55

0.70 0.60 0.22 0.26 0.29

TMS

240 256 346 361

100 7.56 31.6 15.7

0.62 0.67 0.51 0.28

243 259 349 364

100 7.98 36.8 19.0

0.75 1.89 1.00 0.99

a–d


Table I-13. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Cocaine/cocaine-d3 CD Groupc None

a–d

Cocaine Ion (m/z)d Rel. int. 82 182 198 272 303

91.1 100 11.9 10.6 26.4

Analog’s cont. 4.15 0.82 0.99 1.10 0.65

Cocaine-d3 Ion (m/z)d Rel. int. 85 185 201 275 306

94.3 100 9.98 10.5 26.0



Analog’s cont. 0.42 0.10 0.73 0.70 0.36

403

Table I-14a. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Cocaethylene/cocaethylene-d3 CD Groupc None

a–d

Cocaethylene Ion (m/z)d Rel. int. Analog’s cont. 82 196 212 272 317

100 96.9 12.6 18.0 27.8

3.20 0.81 1.01 0.45 0.56

Cocaethylene-d3 Ion (m/z)d Rel. int. Analog’s cont. 85 199 215 275 320

100 96.2 10.1 18.0 28.4

0.48 0.14 0.72 0.29 0.37


Table I-14b. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Cocaethylene/cocaethylene-d8 CD Groupc None

a–d

Cocaethylene Ion (m/z)d Rel. int. Analog’s cont. 82 196 212 272 317

100 96.6 12.6 18.0 27.8

2.83 0.07 0.08 0.09 0.07

Cocaethylene-d8 Ion (m/z)d Rel. int. Analog’s cont. 85 204 220 275 325

100 94.5 9.92 14.4 26.8

0.48 0.07 0.03 0.34 0.04


Table I-15. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Ecgonine methyl ester/ecgonine methyl ester-d3 CD Groupc

Ecgonine methyl ester Ion (m/z)d Rel. int. Analog’s cont.

Ecgonine methyl ester-d3 Ion (m/z)d Rel. int. Analog’s cont.

None

82 96 182 199

100 68.1 8.24 15.6

— 4.40 2.60 2.26

85 99 185 202

100 69.8 7.83 15.2

— 0.86 1.02 0.12

TFA

182 264 295

100 12.7 25.3

4.78 0.72 0.47

185 267 298

100 13.4 24.0

0.12 3.79 0.18

PFP

182 314 345

100 11.2 20.3

4.60 0.16 0.19

185 317 348

100 12.0 21.8

0.09 4.18 0.17

HFB

182 364 395

100 11.7 19.4

— 0.15 0.21

185 367 398

100 11.4 18.7

— 3.79 0.18

TMS

82 83 96 271

100 85.9 75.5 12.4

4.40 2.68 1.81 0.51

85 86 99 274

100 66.1 73.9 11.2

1.57 0.41 1.56 0.98

t-BDMS

82 83 96 182 256 313

100 54.9 41.2 26.5 22.1 5.37

2.54 2.63 2.25 0.96 0.52 0.55

85 86 99 185 259 316

100 45.2 42.5 25.7 20.1 4.46

1.71 0.67 2.57 3.67 0.73 0.94

a–d




404

Table I-16a. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Benzoylecgonine/benzoylecgonine-d3 CD Groupc

Benzoylecgonine Ion (m/z)d Rel. int. Analog’s cont.

Benzoylecgonine-d3 Ion (m/z)d Rel. int. Analog’s cont.

Methyl

82 83 182 198 272 303

83.6 33.4 100 12.4 10.4 26.2

3.51 3.93 3.60 0.31 0.10 0.12

85 86 185 201 275 306

83.5 22.3 100 9.82 10.3 26.4

1.42 0.72 0.08 0.59 0.75 0.29

Ethyl

82 196 212 272 317

79.7 100 13.2 18.9 29.7

2.81 2.63 0.33 0.12 0.13

85 199 215 275 320

89.4 100 10.8 20.2 32.5

0.52 0.09 0.45 0.28 0.33

Propyl

82 210 226 272 331

86.2 100 13.8 21.4 22.7

2.15 0.44 0.23 0.18 0.17

85 213 229 275 334

98.9 100 10.9 21.1 21.7

0.41 0.12 0.21 0.22 0.38

Butyl

82 224 240 272 345

100 99.1 14.6 20.6 25.5

2.32 2.19 0.13 0.10 0.11

85 227 243 275 348

92.1 100 12.1 22.4 29.8

0.49 0.12 0.54 0.20 0.30

Pentafluoro-1propoxy

82 272 300 316 421

47.0 13.0 100 13.0 21.2

3.01 1.75 0.25 0.19 0.12

85 275 303 319 424

56.8 12.7 100 9.60 19.6

0.26 0.69 0.11 0.17 0.32

Hexafluoro2-propoxy

164 272 318 334 439

11.5 9.65 100 12.6 20.5

1.21 0.55 — 0.39 0.10

167 275 321 337 442

11.8 9.51 100 9.71 20.5

3.35 0.68 — 0.15 0.20

TMS

82 240 256 346 361

100 71.6 11.6 7.59 21.7

1.95 0.73 0.45 1.03 0.18

85 243 259 349 364

100 71.9 9.36 7.53 21.5

0.52 0.76 0.89 1.37 1.36

t-BDMS

82 83 282 298 346 403

100 35.5 51.7 9.15 40.7 28.6

2.36 4.03 2.52 0.25 0.12 0.15

85 86 285 301 349 406

100 25.3 45.0 6.21 31.9 20.2

0.67 0.80 0.97 1.43 1.31 1.41

a–d


Table I-16b. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Benzoylecgonine/benzoylecgonine-d8 CD Groupc Methyl

Benzoylecgonine Ion (m/z)d Rel. int. Analog’s cont. 182 198 272 303

100 12.4 10.4 26.2

3.86 0.83 0.09 0.08

Benzoylecgonine-d8 Ion (m/z)d Rel. int. Analog’s cont. 185 201 280 311

100 9.98 10.1 25.2



0.15 0.54 0.10 0.02

405

Table I-16b. (Continued) CD Groupc

Benzoylecgonine Ion (m/z)d Rel. int. Analog’s cont.

Benzoylecgonine-d8 Ion (m/z)d Rel. int. Analog’s cont.

Ethyl

196 212 272 317

100 13.2 18.9 29.7

2.38 0.57 0.06 0.07

199 215 280 325

100 10.6 20.4 33.8

0.13 0.44 0.08 0.04

Propyl

82 210 226 272 331

— 100 13.8 21.4 22.7

— 0.25 0.25 0.11 0.12

85 213 229 280 339

95.4 100 11.1 20.5 21.7

— 0.14 0.22 0.06 0.18

Butyl

105 224 240 272 345

37.5 99.1 14.6 20.6 25.5

1.69 2.68 0.21 0.06 0.06

110 227 243 280 353

32.7 100 12.2 22.1 29.5

4.86 0.17 0.62 0.07 0.01

PFPoxy

300 316 421

100 13.0 21.2

0.23 0.17 0.05

303 319 429

100 9.75 19.3

0.10 0.16 0.11

HFPoxy

164 272 334 439

11.5 9.65 12.6 20.5

0.89 0.29 0.33 0.01

167 280 337 447

13.3 9.26 10.3 24.1

4.73 0.08 0.16 0.00

TMS

82 122 240 256 346

— 10.3 71.6 11.6 7.59

— 4.43 0.66 0.40 0.16

85 125 243 259 354

100 8.73 72.6 9.54 7.86

— 1.81 0.79 1.00 0.24

t-BDMS

82 204 282 346 403

— 20.9 51.7 40.7 28.6

— 0.24 2.63 0.06 0.05

85 212 285 354 411

100 13.9 50.9 39.6 27.5

— 1.93 0.78 0.01 0.00

a–d


Table I-17. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Ecgonine/ecgonine-d3 CD Groupc

Ecgonine Ion (m/z)d Rel. int.

Analog’s cont.

Ecgonine-d3 Ion (m/z)d Rel. int.

Analog’s cont.

[TMS]2

82 83 96 212 329

96.3 100 59.3 9.21 8.99

5.00 3.00 3.27 3.19 0.86

85 86 99 215 332

100 76.6 58.2 8.66 8.53

1.10 0.28 1.69 3.84 1.80

[t-BDMS]2

82 83 96 356 357 413

100 69.2 29.2 42.3 12.8 2.80

1.92 2.04 3.59 0.49 1.44 0.49

85 86 99 359 360 416

100 56.0 29.8 38.2 11.7 2.54

2.16 0.45 4.71 2.47 1.59 3.61

HFPoxy/TFA

264 318 431

11.6 100 18.4

0.81 1.75 0.89

267 321 434

11.5 100 17.2

1.53 0.09 0.19



406


Ecgonine Ion (m/z)d Rel. int.

Analog’s cont.

Ecgonine-d3 Ion (m/z)d Rel. int. Analog’s cont.

PFPoxy/PFP

300 314 463

100 12.8 14.9

2.47 1.03 0.56

303 317 466

100 13.0 14.2

0.09 2.35 0.21

HFPoxy/HFB

318 364 531

100 10.6 11.6

2.87 0.62 0.67

321 367 534

100 10.5 11.1

0.10 0.17 0.25

a–d


Table I-18. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Anhydroecgonine methyl ester/anhydroecgonine methyl ester-d3 CD Groupc None a–d

Anhydroecgonine methyl ester Ion (m/z)d Rel. int. Analog’s cont. 152 181

100 33.5

1.99 1.58

Anhydroecgonine methyl ester-d3 Ion (m/z)d Rel. int. Analog’s cont. 155 184

100 34.9

0.15 0.11


Table I-19. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Caffeine/caffeine-13C3 CD Group

c

None a–d

Ion

Caffeine Rel. int.

Analog’s cont.

46.7 100

3.84 2.93

(m/z)d

109 194

Caffeine-13C3 Ion (m/z)d Rel. int. Analog’s cont. 111 197

43.1 100

2.68 0.23


Table I-20. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Methylphenidate/methylphenidate-d3 CD Groupc

Methylphenidate Ion (m/z)d Rel. int. Analog’s cont.

Methylphenidate-d3 Ion (m/z)d Rel. int. Analog’s cont.

None

150

1.85

—

153

2.01

—

TFA

150

7.94

0.69

153

7.61

3.83

PFP

150

5.66

0.41

153

5.71

1.76

HFB

150

3.74

1.98

153

3.69

3.32

4-CB

438

3.19

0.15

441

2.74

0.31

TMS

59

3.24

—

62

0.60

—

a–d




407

Table I-21. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Ritalinic acid/ritalinic acid-d5 CD Groupc

Ritalinic acid Ion (m/z)d Rel. int. Analog’s cont.

4-CB

424 452

[TMS]2

118

t-BDMS

91 137 165 193 194

a–d

1.09 3.49

0.46 0.27

429 457

1.27 2.92

2.36

—

123

2.29

—

12.4 6.28 4.70 100 16.6

0.42 2.71 0.64 0.23 0.18

96 142 170 198 199

13.6 6.10 4.03 100 16.6

0.12 0.00 0.00 0.00 0.00




Ritalinic acid-d5 Ion (m/z)d Rel. int. Analog’s cont. 1.97 0.00

409

Summary of Drugs, Isotopic Analogs, and Chemical Derivatization Groups Included in Table II (Opioids) Compound

Chemical derivatization groupa

Isotopic analog

Table #

Heroin

d3 , d 9

None

II-1

6-Acetylmorphine

d3 , d 6

None, Acetyl, TFA, propionyl, PFP, HFB, TMS, t-BDMS

II-2

Morphine

d3 , d 6

Ethyl, propyl, butyl, [acetyl]2, [TFA]2, propionyl, [propionyl]2, [PFP]2, [HFB]2, [TMS]2, t-BDMS, [t-BDMS]2, ethyl/acetyl, ethyl/TMS, propyl/TMS, propyl/t-BDMS, butyl/TMS, butyl/t-BDMS, acetyl/TMS, acetyl/t-BDMS, propionyl/TMS

II-3

Hydromorphone

d3 , d 6

Acetyl, [acetyl]2, [TFA]2, propionyl, PFP, [PFP]2, HFB, [HFB]2, TMS, [TMS]2, t-BDMS, [t-BDMS]2, MA/ethyl, MA/acetyl, MA/propionyl, MA/TMS, MA/t-BDMS, HA/[TMS]2

II-4

Oxymorphone

d3

[acetyl]2, [acetyl]3, [TFA]2, propionyl, [propionyl]2, [propionyl]3, [PFP]2, [HFB]2, [TMS]2, II-5 [TMS]3, t-BDMS, MA/ethyl, MA/acetyl, MA/[acetyl]2, MA/propionyl, MA/[HFB]2, MA/ [TMS]2, MA/[t-BDMS]2, MA/ethyl/propionyl, MA/ethyl/TMS, MA/ethyl/t-BDMS, MA/acetyl/TMS, MA/propionyl/TMS, HA/[TMS]3 , HA/[ethyl]2/propionyl, HA/[ethyl]2/TMS

6-Acetylcodeine

d3

None

II-6

Codeine

d3, d6, 13C1d3

None, acetyl, TFA, propionyl, PFP, HFB, TMS, t-BDMS

II-7

Hydrocodone

d3 , d 6

None, ethyl, acetyl, TMS, t-BDMS, MA, HA/TMS

II-8

Dihydrocodeine

d3 , d 6

None, acetyl, TFA, propionyl, PFP, HFB, TMS, t-BDMS

II-9

Oxycodone

d3 , d 6

None, acetyl, [acetyl]2, propionyl, TMS, [TMS]2, t-BDMS, [t-BDMS]2, MA, MA/propionyl, II-10 MA/TMS, HA/[propionyl]2, HA/[TMS]2, HA/ethyl/propionyl

Noroxycodone

d3

None, [acetyl]2, [TFA]3, propionyl, [PFP]2, [HFB]2, [TMS]2, [TMS]3, MA/ethyl, MA/acetyl, II-11 MA/[TFA]2, MA/propionyl, MA/PFP, MA/[HFB]2, MA/[TMS]2, MA/t-BDMS, MA/ethyl/ propionyl, MA/ethyl/TMS, MA/ethyl/t-BDMS, MA/acetyl/TMS, MA/propionyl/TMS, HA/[ethyl]2/TMS

Buprenorphine

d4

Methyl, ethyl, acetyl, MBTFA, PFP, HFB, TMS, [TMS]2, t-BDMS

II-12

Norbuprenorphine

d3

[Methyl]2, [ethyl]2, [acetyl]2, [MBTFA]2, [PFP]2, [HFB]2, [TMS]2, [TMS]3, t-BDMS

II-13

Fentanyl

d5

None

II-14

Norfentanyl

d5

None, acetyl, TCA, TFA, PFP, HFB, 4-CB, TMS, t-BDMS

II-15

Methadone

d3 , d 9

None

II-16

EDDP

d3

None

II-17

Propoxyphene

d5, d7, d11

None

II-18

Norpropoxyphene

d5

None

II-19

Meperidine

d4

None

II-20

Normeperidine

d4

None, ethyl, propyl, butyl, acetyl, TCA, TFA, PFP, HFB, 4-CB, TMS, t-BDMS

II-21

a

MA: methoxyimino; HA: hydroxylimino.

Tanle II — Opioids


411

Appendix Two — Table II Cross-Contributions Between ions Designating the Drugs and Their Isotopically Labeled Analogs in Various Derivatization Forms — Opioids Table II-1a. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Heroin/heroin-d3 ............................................................................................................................. 413 Table II-1b. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Heroin/heroin-d9 ............................................................................................................................. 413 Table II-2a. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — 6-Acetylmorphine/6-acetylmorphine-d3 ........................................................................................ 413 Table II-2b. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — 6-Acetylmorphine/6-acetylmorphine-d6 ........................................................................................ 414 Table II-3a. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Morphine/morphine-d3 ................................................................................................................... 415 Table II-3b. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Morphine/morphine-d6 ................................................................................................................... 416 Table II-4a. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Hydromorphone/hydromorphone-d3 .............................................................................................. 418 Table II-4b. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Hydromorphone/hydromorphone-d6 .............................................................................................. 419 Table II-5. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Oxymorphone/oxymorphone-d3 ..................................................................................................... 420 Table II-6. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — 6-Acetylcodeine/6-acetylcodeine-d3 .............................................................................................. 422 Table II-7a. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Codeine/codeine-d3 ........................................................................................................................ 422 Table II-7b. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Codeine/codeine-d6 ........................................................................................................................ 423 Table II-7c. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Codeine/codeine-13C1-d3 ................................................................................................................ 423 Table II-8a. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Hydrocodone/hydrocodone-d3 ....................................................................................................... 424 Table II-8b. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Hydrocodone/hydrocodone-d6 ....................................................................................................... 425 Table II-9a. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Dihydrocodeine/dihydrocodeine-d3 ............................................................................................... 425 Table II-9b. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Dihydrocodeine/dihydrocodeine-d6 ............................................................................................... 426 Table II-10a. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Oxycodone/oxycodone-d3 .............................................................................................................. 427 Table II-10b. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Oxycodone/oxycodone-d6 .............................................................................................................. 428 Table II-11. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Noroxyocodone/noroxyocodone-d3 ............................................................................................... 429



412

Table II-12. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Buprenorphine/buprenorphine-d4 ................................................................................................... 430 Table II-13. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Norbuprenorphine/norbuprenorphine-d3 ........................................................................................ 431 Table II-14. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Fentanyl/fentanyl-d5 ....................................................................................................................... 432 Table II-15. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Norfentanyl/norfentanyl-d5 ............................................................................................................ 432 Table II-16a. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Methadone/methadone-d3 ............................................................................................................... 433 Table II-16b. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Methadone/methadone-d9 ............................................................................................................... 433 Table II-17. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — EDDP/EDDP-d3 ............................................................................................................................. 433 Table II-18a. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Propoxyphene/propoxyphene-d5 .................................................................................................... 434 Table II-18b. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Propoxyphene/propoxyphene-d7 .................................................................................................... 434 Table II-18c. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Propoxyphene/propoxyphene-d11 ................................................................................................. 434 Table II-19. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Norpropoxyphene/norpropoxyphene-d5 ......................................................................................... 434 Table II-20. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Meperidine/meperidine-d4 .............................................................................................................. 434 Table II-21. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Normeperidine/normeperidine-d4 .................................................................................................. 435



413

Table II-1a. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Heroin/heroin-d3 CD Groupc None

a–d

Heroin Ion (m/z)d Rel. int. Analog’s cont. 215 268 327 328 369

30.6 57.8 100 21.1 70.5

3.75 2.62 0.95 3.89 0.73

Heroin-d3 Ion (m/z)d Rel. int. Analog’s cont. 218 271 330 331 372

29.3 56.2 100 21.4 71.9

1.86 1.41 0.32 0.16 0.42


Table II-1b. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Heroin/heroin-d9 CD Groupc None

a–d

Heroin Ion (m/z)d Rel. int. Analog’s cont. 268 310 327 369

58.0 51.0 100 69.0

1.82 0.02 0.12 0.00

Heroin-d9 Ion (m/z)d Rel. int. Analog’s cont. 272 316 334 378

64.0 76.0 100 81.0

0.19 0.01 0.01 0.00


Table II-2a. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — 6-Acetylmorphine/6-acetylmorphine-d3 CD Groupc

6-Acetylmorphine Ion (m/z)d Rel. int. Analog’s cont.

6-Acetylmorphine-d3 Ion (m/z)d Rel. int. Analog’s cont.

None

268 327 328

89.7 100 22.8

2.07 1.04 2.29

271 330 331

86.1 100 20.5

0.61 0.24 0.23

Acetyl

215 268 310 327 369

38.1 69.6 55.9 100 68.6

3.76 2.61 0.61 0.93 0.49

218 271 313 330 372

36.7 68.8 56.7 100 68.9

1.85 1.10 0.64 0.34 0.45

TFA

204 311 364 380 423

29.4 29.0 100 10.4 61.2

2.66 1.77 1.36 1.57 1.14

207 314 367 383 426

31.6 29.6 100 10.6 57.1

4.69 0.47 0.49 0.64 0.44

Propionyl

215 268 383 384

20.2 49.7 50.7 12.5

3.51 2.48 0.19 2.50

218 271 386 387

19.6 47.6 51.2 12.7

1.91 1.65 0.47 0.18

PFP

361 414 473

30.1 100 57.1

3.55 3.16 2.87

364 417 476

29.9 100 57.2

0.36 0.47 0.21



414

Table II-2a. (Continued) CD Groupc



HFB

411 464 480 523

30.9 100 10.6 54.1

1.79 1.56 1.75 1.19

414 467 483 526

29.8 100 10.5 53.7

0.45 0.51 0.69 0.50

TMS

399

100

2.13

402

100

1.38

t-BDMS

342 441 442

100 61.4 20.6

0.75 0.20 2.42

345 444 445

100 65.4 21.6

1.14 1.72 0.77

a–d


Table II-2b. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — 6-Acetylmorphine/6-acetylmorphine-d6 CD Groupc



None

268 327 328

89.7 100 22.8

1.87 1.38 1.15

271 333 334

100 91.6 20.7

2.06 0.04 0.00

Acetyl

215 268 310 327 369

38.1 69.6 55.9 100 68.6

4.01 1.49 0.34 0.39 0.30

218 271 313 333 375

38.4 69.3 58.1 100 68.0

1.80 1.11 0.67 0.04 0.04

TFA

311 364 380 423

29.0 100 10.4 61.2

0.87 0.31 0.42 0.02

314 367 383 429

28.3 100 6.78 58.6

1.33 1.35 2.68 0.09

Propionyl

215 268 383 384

20.2 49.7 50.7 12.5

3.66 1.72 0.15 0.19

218 271 389 390

21.7 51.0 50.1 12.5

2.10 1.78 0.00 0.00

PFP

361 414 430 473

30.1 100 10.4 57.1

3.40 2.77 4.05 2.54

364 417 433 479

29.3 100 7.08 55.6

2.63 2.33 4.04 0.00

HFB

411 464 480 523

30.9 100 10.6 54.1

3.10 2.50 2.81 2.18

414 467 483 529

30.4 100 6.79 51.4

1.76 1.86 3.24 0.00

TMS

399

100

4.96

405

100

0.05

t-BDMS

342 384 441 442

100 42.5 61.4 20.6

0.80 2.95 0.12 0.14

346 390 447 448

100 48.3 73.9 25.0

0.17 0.00 0.00 0.00

a–d




415

Table II-3a. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Morphine/morphine-d3 CD Groupc

Morphine Ion (m/z)d Rel. int. Analog’s cont.

Morphine-d3 Ion (m/z)d Rel. int. Analog’s cont.

Ethyl

313

100

1.27

316

100

0.38

Propyl

327

100

0.47

330

100

0.30

Butyl

341 342

100 23.3

0.77 0.09

344 345

100 23.5

0.32 0.13

[Acetyl]2

215 268 310 327 369

36.8 67.6 55.1 100 66.6

3.49 2.16 0.42 0.59 0.32

218 271 313 330 372

38.5 67.7 57.0 100 67.8

1.81 1.05 0.53 0.31 0.44

[TFA]2

311 364 380 458 477

6.24 100 6.32 1.51 37.4

1.43 0.17 0.35 0.00 0.13

314 367 383 461 480

6.54 100 6.51 1.80 37.9

0.42 0.29 0.39 2.31 0.41

Propionyl

268 341

95.0 100

2.43 2.47

271 344

89.1 100

0.45 0.37

[Propionyl]2

268 324 341 342 397

51.1 39.7 100 22.0 45.9

1.82 0.28 0.48 4.13 0.25

271 327 344 345 400

48.0 39.7 100 22.5 48.1

0.96 2.55 0.34 0.19 0.53

[PFP]2

361 414 430 558 577

5.35 100 6.98 3.77 26.1

1.45 0.31 0.94 0.00 0.28

364 417 433 561 580

5.40 100 7.11 3.95 26.2

5.45 0.33 0.34 1.71 0.56

[HFB]2

266 411 464 480 658 677

4.41 5.36 100 7.42 5.19 18.0

4.06 2.41 1.46 1.43 1.22 1.38

269 414 467 483 661 680

4.56 5.43 100 8.15 5.94 18.8

2.33 0.71 0.35 0.43 1.16 0.61

[TMS]2

236 401 429

57.8 25.8 100

— 2.89 0.48

239 404 432

54.3 26.2 100

— 2.88 3.50

t-BDMS

342 399

100 53.8

3.08 0.65

345 402

100 52.1

1.14 1.58

[t-BDMS]2

146 456 485 513

17.9 53.2 3.92 6.51

— 2.08 0.00 0.00

149 459 488 516

18.4 46.7 3.94 6.24

— 4.31 0.00 0.00

Ethyl/acetyl

243 296 326 355

21.3 56.8 15.6 100

4.65 0.81 0.46 0.37

246 299 329 358

20.2 53.7 14.0 100

0.58 1.98 0.51 0.36

Ethyl/TMS

146 357 385 386

37.6 26.8 100 29.5

1.50 4.04 0.18 1.78

149 360 388 389

37.0 26.4 100 29.9

2.11 1.40 1.65 0.78

Propyl/TMS

206 146 196 371 399

60.2 39.7 46.1 28.1 100

— 1.98 3.92 0.74 0.16

209 149 199 374 402

51.9 34.3 39.5 27.3 100

— 2.25 4.60 1.44 1.64



416




Propyl/t-BDMS

146 384 398 441

39.2 64.5 9.02 10.7

4.15 0.00 0.00 0.00

149 387 401 444

33.0 71.2 9.05 11.9

2.59 0.00 0.00 0.00

Butyl/TMS

220 146 234 385 413

63.9 41.5 42.1 29.8 100

— 2.98 2.90 3.03 1.44

223 149 237 388 416

64.1 43.1 43.1 28.9 100

— 2.87 4.29 2.37 1.80

Butyl/t-BDMS

398 427 455

85.1 8.36 17.1

0.00 0.00 0.00

401 430 458

79.9 7.52 16.2

0.00 0.00 0.00

Acetyl/TMS

324 399

10.5 100

3.16 0.51

327 402

11.1 100

0.86 3.17

Acetyl/t-BDMS

342 441 442

100 70.6 22.8

1.46 0.94 3.59

345 444 445

100 73.4 24.5

1.15 1.58 0.79

Propionyl/TMS

357 413

100 78.0

1.92 0.36

360 416

100 82.1

1.12 1.43

a–d


Table II-3b. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Morphine/morphine-d6 CD Groupc



Ethyl

284 313 314

24.5 100 20.9

4.87 1.47 2.04

290 319 320

22.8 100 21.8

0.12 0.04 0.23

Propyl

284 327 328

23.9 100 22.7

1.70 0.60 1.02

290 333 334

22.7 100 22.4

0.36 0.02 0.00

Butyl

341 342

100 23.3

0.21 0.22

347 348

100 23.4

0.05 0.09

[Acetyl]2

268 284 310 327 369

67.6 9.18 55.1 100 66.6

1.75 0.95 0.41 0.35 0.32

274 290 316 333 375

68.9 8.64 60.0 100 68.0

0.02 0.00 0.00 0.00 0.00

[TFA]2

311 364 380 477

6.24 100 6.32 37.4

2.77 0.12 0.24 0.09

317 370 386 483

6.70 100 6.21 34.9

1.22 0.00 0.07 0.00

Propionyl

268 341 342

95.0 100 21.3

1.87 2.15 2.60

274 347 348

91.4 100 2.00

0.00 0.00 0.00

[Propionyl]2

268 324 341 342 397

51.1 39.7 100 22.0 45.9

2.69 0.21 0.32 0.84 0.19

274 330 347 348 403

48.8 40.6 100 22.1 46.8

0.03 0.03 0.00 0.00 0.02



417

Table II-3b. (Continued) CD Groupc



[PFP]2

361 414 430 577

5.35 100 6.98 26.1

3.51 0.84 1.66 0.78

367 420 436 583

5.54 100 6.92 26.0

1.27 0.00 0.02 0.00

[HFB]2

266 464 480 658 677

4.41 100 7.42 5.19 18.0

4.39 3.88 3.64 3.78 3.74

272 470 486 664 683

3.79 100 8.14 6.41 20.5

1.13 0.01 0.00 2.94 0.00

[TMS]2

236 324 401 414 429

57.8 18.2 25.8 44.9 100

— 3.69 2.44 1.30 1.02

239 330 404 420 435

60.7 17.3 30.6 42.4 100

— 2.36 2.85 0.00 0.00

t-BDMS

162 342 399

22.8 100 53.8

3.87 3.03 0.65

168 348 405

20.6 100 51.8

4.87 0.07 0.00

[t-BDMS]2

413 146 456 513

61.8 17.5 53.2 6.51

— 2.76 1.27 0.00

415 149 462 519

63.8 20.4 54.0 6.75

— 4.73 0.00 0.00

Ethyl/acetyl

266 296 312 326 355 356

15.9 76.3 9.75 19.6 100 19.4

0.00 0.00 0.00 0.00 3.50 4.27

272 302 318 332 361 362

12.9 82.3 10.6 15.8 100 27.5

0.00 0.00 0.00 0.00 0.00 0.00

Ethyl/TMS

146 357 385 386

37.6 26.8 100 29.5

2.96 1.13 0.09 0.30

149 360 391 392

44.1 28.6 100 30.4

2.43 1.53 0.11 0.14

Propyl/TMS

206 146 371 399

60.2 39.7 28.1 100

– 2.74 0.56 0.09

209 149 374 405

59.7 38.3 29.7 100

— 2.55 1.49 0.04

Propyl/t-BDMS

384 441

64.5 10.7

0.00 0.00

390 447

59.1 15.2

0.00 0.00

Butyl/TMS

220 146 385 413

63.9 41.5 29.8 100

— 3.54 2.52 0.97

223 149 388 419

71.0 45.3 32.6 100

— 3.19 2.57 0.48

Butyl/t-BDMS

398 455

85.1 17.1

0.00 0.00

404 461

67.8 6.41

0.00 0.00

Acetyl/TMS

287 340 399

47.2 75.8 98.3

2.48 0.00 0.00

293 346 405

37.7 71.3 79.7

4.69 0.00 0.00

Acetyl/t-BDMS

342 343 384 441

100 24.7 45.6 50.2

0.00 0.00 0.00 0.00

348 349 388 447

100 28.0 36.5 48.3

0.00 0.00 0.00 0.00

Propionyl/TMS

384

64.5

—

390

59.1

—

a–d

See the corresponding footnotes in Table I-1a. Tanle II — Opioids


418

Table II-4a. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Hydromorphone/hydromrophone-d3 CD Groupc

Hydromorphone Ion (m/z)d Rel. int. Analog’s cont.

Hydromorphone-d3 Ion (m/z)d Rel. int. Analog’s cont.

Acetyl

256 285 327

10.3 100 26.3

4.52 2.40 1.84

259 288 330

10.2 100 26.7

3.47 0.37 0.41

[Acetyl]2 (enol)

237

100

—

330

100

—

[TFA]2 (enol)

258 364 380 477

36.1 27.3 49.3 100

3.05 1.99 0.36 0.52

261 367 383 480

37.2 27.6 50.4 100

1.21 3.41 0.29 0.37

Propionyl

285

100

—

288

100

—

PFP

431

100

—

434

100

—

[PFP]2 (enol)

308 414 430 577

41.8 37.6 63.9 100

1.74 1.45 0.28 0.52

311 417 433 580

39.3 36.4 63.8 100

1.33 0.62 0.33 0.43

HFB

481

100

—

484

100

—

[HFB]2 (enol)

358 464 480 677

61.5 56.0 100 95.9

3.57 3.06 1.34 1.50

361 467 483 680

60.4 57.9 95.3 100

2.51 3.43 1.62 1.30

TMS

342 357

25.9 100

3.44 0.78

345 360

24.8 100

1.85 1.64

[TMS]2 (enol)

234 429 430

55.3 100 35.5

2.25 0.60 3.59

237 432 433

58.2 100 36.5

4.19 3.77 2.45

t-BDMS

342 399

28.1 7.23

— 2.60

345 402

26.8 6.81

— 2.48

[t-BDMS]2 (enol)

456 513

100 8.27

2.18 3.46

459 516

100 8.39

3.82 4.61

Methoxyimino/ ethyl

342 343

100 21.4

0.62 4.34

345 346

100 21.6

0.31 0.13

Methoxyimino/ acetyl

314 356

100 44.9

0.42 0.00

314 359

100 49.7

0.00 0.00

Methoxyimino/ propionyl

314 370

100 38.9

1.18 0.54

317 373

100 38.3

0.29 0.43

Methoxyimino/ TMS

355 371 386 387

82.7 45.6 100 29.5

1.48 2.25 0.33 2.97

358 374 389 390

80.6 42.0 100 27.0

4.86 1.26 1.34 0.58

Methoxyimino/ t-BDMS

371 428

31.3 11.2

1.41 0.33

374 431

100 33.5

1.33 1.67

Hydroxyimino/ [TMS]2

355 429 444

79.3 34.6 64.8

0.55 1.22 0.00

358 432 447

64.5 37.5 56.5

1.62 2.79 2.91

a–d




419

Table II-4b. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Hydromorphone/hydromorphone-d6 CD Groupc



Acetyl

285 327

100 26.3

1.93 1.65

291 333

100 25.5

0.10 0.04

[Acetyl]2 (enol)

326 327 369

31.4 100 44.5

4.18 1.71 2.45

332 333 375

30.1 100 44.9

0.72 0.07 0.38

[TFA]2 (enol)

258 364 380 476 477

36.1 27.3 49.3 45.6 100

2.57 0.32 0.15 0.08 0.09

264 370 386 482 483

32.7 29.1 55.1 33.1 100

2.27 0.03 0.00 0.00 0.00

Propionyl

285

100

—

291

100

—

PFP

431

100

—

437

100

—

[PFP]2 (enol)

308 414 430 577 578

41.8 37.6 63.9 100 24.1

1.58 0.30 0.05 0.12 1.00

314 420 436 583 584

37.3 39.0 68.9 100 25.3

0.23 0.03 0.02 0.00 0.00

HFB

425

75.9

—

431

72.8

—

[HFB]2 (enol)

464 480 677 678

56.0 100 95.9 25.1

1.35 0.85 0.61 2.87

470 486 683 684

57.4 98.0 100 26.7

0.07 0.04 0.00 0.00

TMS

314 342 357 358

19.7 25.7 100 27.8

3.49 0.87 0.43 1.18

320 348 363 364

17.5 25.9 100 27.9

0.58 0.34 0.16 0.08

[TMS]2 (enol)

184 234 324 414 429 430

24.8 55.3 17.1 91.6 100 35.5

3.42 2.67 3.95 1.71 0.12 0.76

188 240 330 420 435 436

28.0 54.4 18.0 72.8 100 36.3

1.86 3.62 3.08 0.11 0.14 0.11

t -BDMS

299 342 399

100 28.1 7.23

— 2.91 1.35

301 348 405

100 28.0 6.86

— 0.66 0.59

[t-BDMS]2 (enol)

456 457 513

100 38.4 8.23

1.75 4.51 3.18

462 463 519

100 38.1 7.85

0.32 0.33 0.60

Methoxyimino/ ethyl

311 342 343

85.0 100 21.4

0.39 0.12 1.20

317 348 349

85.7 100 23.1

0.02 0.00 0.00


283 314 325 356

79.8 100 19.5 44.9

0.55 0.31 0.00 0.00

289 320 331 362

75.1 100 15.5 42.3

0.00 0.00 0.00 0.00


283 314 315 339 370

58.7 100 20.8 9.48 38.9

0.56 0.50 2.32 0.22 0.12

289 320 321 345 376

58.4 100 20.9 9.24 37.3

0.04 0.00 0.21 0.31 0.01



420

Table II-4b. (Continued) CD Groupc



Methoxyimino/ TMS

355 356 371 386 387

90.7 24.5 40.3 100 29.7

5.60 7.88 0.83 0.06 1.37

361 362 377 392 393

86.4 24.0 41.3 100 41.3

0.09 0.10 0.14 0.06 0.04


371 397 428

31.3 5.45 11.2

1.36 0.24 0.04

377 403 434

100 15.0 32.9

0.09 0.44 0.00

Hydroxyimino/ [TMS]2

339 355 356 429 444

12.5 79.3 19.7 34.6 64.8

0.00 0.00 3.47 0.08 0.00

345 361 362 435 450

8.63 59.8 15.2 34.4 48.6

1.16 0.75 0.83 0.00 0.00

a–d


Table II-5. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Oxymorphone/oxymorphone-d3 CD Groupc

Oxymorphone Ion (m/z)d Rel. int. Analog’s cont.

Oxymorphone-d3 Ion (m/z)d Rel. int. Analog’s cont.

[Acetyl]2

300 343 344 385

37.6 100 21.4 30.4

2.10 1.31 2.82 1.08

303 346 347 388

37.6 100 21.1 31.0

0.50 0.45 0.41 0.51

[Acetyl]3 (enol)

342 385 386 427

23.9 100 23.5 54.1

1.78 0.72 1.61 0.74

345 388 389 430

23.1 100 23.4 54.0

0.87 0.43 0.32 0.85

[TFA]2

396 493

26.6 100

2.01 1.72

399 496

26.0 100

0.89 0.50

Propionyl

301

100

—

304

100

—

[Propionyl]2

357

100

—

360

100

—

[Propionyl]3 (enol)

356 396 413 414 469

15.5 6.88 100 25.2 33.7

3.42 2.66 2.15 3.38 1.99

359 399 416 417 472

14.9 7.26 100 25.0 34.6

2.11 2.48 1.67 1.37 1.85

[PFP]2

446 593

33.1 100

2.62 2.64

449 596

37.5 100

0.43 0.52

[HFB]2

308 496 693

21.0 52.5 100

2.88 3.16 3.38

311 499 696

19.5 56.7 100

1.67 0.80 0.64

[TMS]2

430 445 446

20.6 100 36.2

1.82 0.34 1.86

433 448 449

20.6 100 35.8

2.80 2.84 1.74

[TMS]3 (enol)

502 518

77.0 40.4

— 2.45

505 521

73.6 39.1

— 3.07

t-BDMS

358

100

4.89

361

100

1.50



421

Table II-5. (Continued) CD Groupc

Oxymorphone Ion (m/z)d Rel. int. Analog’s cont.

Oxymorphone-d3 Ion (m/z)d Rel. int. Analog’s cont.

Methoxyimino/ ethyl

329 358 359

10.1 100 24.1

1.65 0.00 0.00

332 361 362

11.8 100 21.7

0.07 0.00 0.03


329 341 355 372

19.9 6.75 9.07 100

4.26 0.00 0.00 0.03

332 344 358 375

14.8 6.15 7.25 100

0.00 0.00 0.00 0.00

Methoxyimino/ [acetyl]2

329 341 355 371 372 414

17.8 6.20 6.89 25.6 100 70.4

0.00 0.00 0.00 0.00 0.00 0.00

332 344 358 374 375 417

19.6 5.10 6.92 25.8 100 65.1

0.33 0.00 3.28 0.00 0.40 0.53


299 355 386

23.0 7.97 53.0

1.85 0.00 4.22

302 358 389

11.9 4.61 51.4

0.00 0.00 0.00

Methoxyimino/ [HFB]2

412 477 509 525 722

16.9 4.00 5.47 18.0 16.9

0.00 0.00 0.00 0.00 0.00

415 480 512 528 725

15.3 3.19 4.22 17.3 15.4

0.00 0.00 0.00 0.00 0.00

Methoxyimino/ [TMS]2

459 474 475

14.6 100 36.5

0.69 0.17 1.72

462 477 478

15.2 100 38.1

2.90 3.25 1.86

Methoximino/ [t-BDMS]2

440 501 558

34.5 57.0 5.96

0.00 0.00 0.00

443 504 561

23.2 71.2 9.04

0.00 0.00 0.00

Methoxyimino/ ethyl/propionyl

244 341 357 385 414 415

25.6 7.94 35.1 21.2 100 24.5

4.32 3.84 1.32 0.36 0.00 1.32

247 344 360 388 417 418

22.1 8.75 33.0 21.4 100 25.5

0.75 0.92 0.33 0.42 0.58 0.17

Methoxyimino/ ethyl/TMS

415 430

14.7 100

0.64 0.06

418 433

12.1 100

1.31 1.31

Methoxyimino/ ethyl/t-BDMS

329 358 359

10.1 100 24.1

1.65 0.00 0.00

332 361 362

11.8 100 21.7

0.07 0.00 0.03

Methoxyimino/ acetyl/TMS

215 402 444 445

59.0 62.5 100 30.9

3.98 0.79 0.06 2.86

218 405 447 448

64.9 63.3 100 31.5

2.96 1.38 1.57 0.75

Methoxyimino/ propionyl/TMS

215 402 403 443 458

42.8 100 31.8 15.6 91.9

4.96 0.94 1.88 0.09 0.06

218 405 406 446 461

41.6 100 25.8 18.0 90.8

1.87 1.40 0.70 1.52 1.64

Hydroxylimino/ [TMS]3

459 533

4.44 31.6

0.00 0.64

462 536

4.92 32.1

4.52 2.93

Hydroxylimino/ [ethyl]2/propionyl

371 399 428 429

34.1 23.4 100 30.0

1.79 0.00 2.58 0.00

374 402 431 432

58.7 27.6 100 27.3

0.00 0.00 0.53 0.00



422

Table II-5. (Continued) CD Groupc Hydroxylimino/ [ethyl]2/TMS

a–d

Oxymorphone Ion (m/z)d Rel. int. Analog’s cont. 309 399 429 444 445

5.79 7.97 15.1 100 32.1

0.00 0.00 0.00 0.00 0.00

Oxymorphone-d3 Ion (m/z)d Rel. int. Analog’s cont. 312 402 432 447 448

10.7 10.0 16.4 100 25.9

0.00 0.00 0.00 0.00 0.00


Table II-6. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — 6-Acetylcodeine/6-acetylcodeine-d3 CD Groupc None

a–d

6-Acetylcodeine Ion (m/z)d Rel. int. Analog’s cont. 229 282 341

59.7 100 89.4

3.75 1.45 1.50

6-Acetylcodeine-d3 Ion (m/z)d Rel. int. Analog’s cont. 232 285 344

43.4 85.5 100

0.75 1.58 0.39


Table II-7a. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Codeine/codeine-d3 CD Groupc

Codeine Ion (m/z)d Rel. int.

Analog’s cont.

Codeine-d3 Ion (m/z)d Rel. int.

Analog’s cont.

None

299

100

0.92

302

100

0.25

Acetyl

229 282 298 341 342

39.5 76.5 8.92 100 22.8

4.22 0.98 2.23 0.54 4.24

232 285 301 344 345

37.9 75.9 8.57 100 22.8

0.69 3.10 0.47 0.32 0.14

TFA

282 395

100 83.3

0.64 0.49

285 398

100 81.2

0.36 0.33

Propionyl

229 282 355 356

30.2 71.1 100 23.6

3.46 0.77 0.57 3.88

232 285 358 359

33.2 75.5 100 24.2

0.68 0.54 0.38 0.16

PFP

282 445

100 56.7

2.49 2.31

285 448

100 57.4

0.24 0.37

HFB

282 495

100 62.0

1.96 1.25

285 498

100 66.0

0.25 0.43

TMS

343 371

18.6 100

4.36 0.83

346 374

18.7 100

1.08 1.17

t-BDMS

356 413

49.2 3.21

2.94 2.70

359 416

48.3 2.95

1.23 2.65

a–d




423

Table II-7b. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Codeine/codeine-d6 CD Groupc


Analog’s cont.

Codeine-d6 Ion (m/z)d Rel. int.

Analog’s cont.

None

282 299 300

10.4 100 20.2

2.71 1.01 1.27

288 305 306

11.0 100 21.1

0.05 0.01 0.08

Acetyl

282 298 341 342

76.5 8.92 100 22.8

0.46 0.62 0.35 0.39

288 304 347 348

77.4 8.59 100 23.1

0.02 0.06 0.00 0.00

TFA

266 282 338 395

10.4 100 5.73 83.3

1.95 0.22 1.03 0.13

269 288 341 401

9.70 100 5.45 77.7

3.36 0.02 1.93 0.00

Propionyl

282 298 355 356

71.1 12.8 100 23.6

0.35 0.40 0.37 0.50

288 304 361 362

68.3 8.90 100 23.7

0.01 0.04 0.00 0.00

PFP

282 388 445

100 4.17 56.7

3.37 4.16 3.20

288 391 451

100 4.82 62.3

0.01 0.31 0.00

HFB

282 438 495

100 4.48 62.0

3.14 3.36 2.24

288 441 501

100 4.97 58.2

0.02 0.57 0.05

TMS

371

100

0.40

377

100

0.07

t-BDMS

313 314 356 357

100 25.4 49.2 13.5

0.82 2.00 0.55 2.33

316 317 362 363

100 25.2 49.1 13.6

1.02 0.66 0.00 0.00

a–d


Table II-7c. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Codeine/codeine-13C1d3 CD Groupc


Analog’s cont.

Codeine-13C1d3 Ion (m/z)d Rel. int. Analog’s cont.

None

229 282 299 300

27.8 11.9 100 19.5

3.09 1.29 0.15 1.29

233 286 303 304

26.4 11.1 100 19.8

0.84 1.52 0.13 0.11

Acetyl

229 282 298 341 342

42.4 81.5 9.06 100 22.5

2.67 1.05 2.38 0.61 0.89

233 286 302 345 346

43.7 81.2 9.31 100 21.8

0.67 0.20 0.06 0.04 0.02

TFA

282 283 395 396

100 20.2 50.7 11.1

0.50 1.64 0.16 0.46

286 287 399 400

100 19.1 54.0 11.5

0.13 0.35 0.13 0.10

Propionyl

229 282 355 356

30.2 71.1 100 23.6

1.84 0.48 0.34 0.63

233 286 359 360

32.3 73.9 100 22.7

0.68 0.13 0.04 0.07



424

Table II-7c. (Continued) CD Groupc


Analog’s cont.

Codeine-13C1d3 Ion (m/z)d Rel. int. Analog’s cont.

PFP

282 283 445 446

100 20.5 39.0 9.06

0.49 1.61 0.13 0.49

286 287 449 450

100 19.2 35.3 7.84

0.08 0.10 0.04 0.00

HFB

58 282 283 495 496

28.1 100 20.9 35.6 8.82

0.89 1.45 3.97 0.45 0.59

62 286 287 499 500

27.8 100 19.5 32.3 7.20

0.99 0.04 0.13 0.07 0.00

TMS

178 343 371 372

75.8 21.6 100 29.1

— 1.38 0.13 0.94

182 347 375 376

66.6 21.1 100 28.0

— 0.16 0.17 0.10

t-BDMS

313 356 357

100 45.9 13.4

— 2.55 3.99

316 360 361

100 51.5 12.6

— 0.43 0.33

a–d


Table II-8a. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Hydrocodone/hydrocodone-d3 CD Groupc

Hydrocodone Ion (m/z)d Rel. int. Analog’s cont.

Hydrocodone-d3 Ion (m/z)d Rel. int. Analog’s cont.

None

299

100

2.39

302

100

0.27

Ethyl

282 298 327

21.0 54.6 100

2.28 0.82 0.44

285 301 330

19.4 49.5 100

2.98 0.37 0.17

Acetyl

298 341 342

77.0 100 16.8

0.11 0.00 0.00

301 344 345

79.3 100 24.3

0.00 0.00 0.00

TMS

234 371

60.5 100

1.12 0.34

237 374

66.9 100

2.79 1.19

t-BDMS

276 356 357 398 413

18.2 93.3 27.1 7.28 7.16

0.00 0.00 0.00 0.00 0.00

279 359 360 401 416

16.8 59.7 14.7 4.32 5.44

0.00 0.00 0.00 0.00 0.00

Methoxyimino

297 328

80.7 100

1.91 0.47

300 331

70.9 100

4.75 0.34

Hydroxylimino/ TMS

297 386

100 89.7

1.29 0.19

300 389

100 89.5

0.90 1.31

a–d




425

Table II-8b. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Hydrocodone/hydrocodone-d6 CD Groupc

Hydrocodone Ion (m/z)d Rel. int. Analog’s cont.

Hydrocodone–d6 Ion (m/z)d Rel. int. Analog’s cont.

None

242 256 284 299

48.3 11.1 13.3 100

4.30 4.80 2.70 2.16

245 262 287 305

32.3 7.85 10.2 100

2.97 0.33 1.86 0.04

Ethyl

282 298 312 326 327

21.0 54.6 46.3 21.3 100

1.15 0.79 0.07 0.00 0.05

288 304 315 332 337

19.8 49.3 38.7 25.4 100

0.04 0.04 0.28 0.00 0.00

Acetyl

298 326 341

80.0 22.0 100

0.00 0.00 0.00

304 329 347

96.6 8.95 100

0.00 0.00 0.00

TMS

234 313 356 370 371

60.5 23.1 45.0 36.6 100

2.12 4.46 0.18 0.00 0.00

237 317 359 376 377

61.3 23.1 31.8 37.7 100

3.96 1.61 1.50 0.04 0.00

t-BDMS

313 356 357 398 413

100 93.3 27.1 7.28 7.16

0.00 0.00 0.00 0.00 0.00

316 362 363 401 419

86.1 86.5 22.5 4.47 6.68

0.00 0.00 0.00 0.00 0.00

Methoxyimino

297 298 328 329

80.7 21.6 100 26.8

0.08 0.00 0.00 0.00

303 304 334 335

77.4 16.7 100 20.5

0.00 0.00 0.00 0.00

Hydroxylimino/ TMS

297 298 329 371 386

100 22.4 14.6 18.4 89.7

0.40 2.35 2.27 4.67 0.05

303 304 332 377 392

100 22.7 15.2 13.8 87.7

1.24 1.61 2.89 0.00 0.00

a–d


Table II-9a. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Dihydrocodeine/dihydrocodeine-d3 CD Groupc

Dihydrocodeine Ion (m/z)d Rel. int. Analog’s cont.

Dihydrocodeine–d3 Ion (m/z)d Rel. int. Analog’s cont.

None

301

100

—

304

100

—

Acetyl

300 343 344

30.9 100 22.0

1.17 0.79 4.57

303 346 347

31.1 100 30.9

0.67 0.36 0.12

TFA

284 300 397 398

39.2 13.5 100 23.0

1.53 0.69 0.41 4.46

287 303 400 401

34.2 12.0 100 31.3

0.73 0.28 0.36 0.18

Propionyl

284 357

31.9 100

1.47 0.69

287 360

32.2 100

2.49 0.38



426




PFP

284 300 447

43.7 14.0 100

1.72 1.27 0.72

287 303 450

45.0 14.4 100

0.51 0.52 0.38

HFB

284 300 360 497

43.0 14.5 4.57 10.0

2.17 1.41 1.61 1.01

287 303 363 500

44.3 14.8 4.58 100

0.72 0.84 0.31 0.40

TMS

146 373 374

22.7 100 29.2

3.78 0.37 3.29

149 376 377

20.3 100 38.1

2.54 1.47 0.60

t-BDMS

358

83.0

3.91

361

82.5

1.23

a–d


Table II-9b. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Dihydrocodeine/dihydrocodeine-d6 CD Groupc



None

284 300 301 302

14.0 18.7 100 20.2

0.55 0.62 0.47 0.78

290 306 307 308

14.5 19.9 100 20.2

0.11 0.28 0.05 0.03

Acetyl

284 300 328 343 344

37.2 34.1 8.40 100 22.8

0.46 0.43 0.78 0.40 0.44

290 306 331 349 350

37.7 33.1 5.39 100 22.4

0.08 0.00 0.65 0.00 0.00

TFA

284 300 340 382 397

36.5 12.7 9.74 9.15 100

0.48 0.63 1.62 0.80 0.31

290 306 343 385 403

39.9 13.6 10.5 5.59 100

0.04 0.19 0.44 0.88 0.00

Propionyl

284 300 342 357 358

31.9 38.8 7.23 100 23.4

0.60 0.47 1.12 0.39 0.44

290 306 345 363 364

32.2 32.5 4.63 100 23.9

0.00 0.00 2.73 0.00 0.00

PFP

284 300 390 432 447

43.3 14.2 8.67 8.05 100

2.00 2.55 3.17 2.60 1.83

290 306 393 435 453

44.0 13.6 8.97 4.96 100

0.06 0.11 0.33 1.16 0.00

HFB

497

100

—

503

100

—

TMS

373

100

—

379

100

—

t-BDMS

315 316 358 415

100 27.9 81.8 8.89

0.80 1.64 0.72 2.96

318 319 364 421

100 25.1 79.2 7.93

1.07 0.58 0.00 0.00

a–d




427

Table II-10a. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Oxycodone/oxycodone-d3 CD Groupc

Oxycodone Ion (m/z)d Rel. int. Analog’s cont.

Oxycodone-d3 Ion (m/z)d Rel. int. Analog’s cont.

None

315

100

4.67

318

100

0.52

Acetyl

314 357 358

55.4 100 22.8

1.13 0.61 2.94

317 360 361

53.7 100 23.2

0.38 0.42 0.34

[Acetyl]2 (enol)

356 399

39.5 100

2.57 0.77

359 402

39.3 100

0.90 0.57

Propionyl

298 314 315 371 372

22.5 65.2 14.9 100 23.8

4.25 0.92 2.75 0.86 3.20

301 317 318 374 375

19.9 62.0 14.5 100 23.2

1.03 0.36 0.18 0.44 0.20

TMS

387 388

100 29.7

0.41 1.98

390 391

100 28.7

1.33 0.76

[TMS]2 (enol)

459

100

1.13

462

100

3.11

t-BDMS

372

100

—

375

100

—

[t-BDMS]2 (enol)

486 487 543

78.8 63.7 7.65

1.63 2.23 0.00

489 490 546

99.4 42.2 2.68

1.15 0.00 0.00

Methoxyimino

287 313 344

9.12 12.9 100

0.93 0.39 0.34

290 316 347

10.1 12.4 100

0.63 2.80 0.35


295 343 400

19.4 53.7 100

3.58 1.96 1.79

298 346 403

15.1 40.6 100

0.00 0.00 0.00

Methoxyimino/ TMS

416 417

100 29.9

0.13 1.87

419 420

100 28.2

1.43 0.64

Hydroxylimino/ [propionyl]2

230 295 313 328 386 442

45.0 50.0 14.1 30.3 11.4 21.5

0.00 0.00 0.00 0.00 0.00 0.00

233 298 316 331 389 445

60.2 48.2 17.0 32.1 12.7 20.8

0.00 0.00 0.00 0.00 0.00 0.00


385 474 475

11.0 82.6 32.3

2.03 0.06 0.55

388 477 478

9.67 90.6 33.7

3.75 3.11 1.63

Hydroxylimino/ ethyl/propionyl

357 414 415

43.5 100 20.2

0.00 0.00 0.00

360 417 418

43.1 100 24.0

0.00 0.00 0.00

a–d




428

Table II-10b. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Oxycodone/oxycodone-d6 CD Groupc

Oxycodone Ion (m/z)d Rel. int. Analog’s cont.

Oxycodone-d6 Ion (m/z)d Rel. int. Analog’s cont.

None

315

100

–

321

100

-

Acetyl

298 314 357 358

17.0 55.4 100 22.8

0.76 0.29 0.32 0.49

304 320 363 364

16.0 53.4 100 21.6

0.21 0.02 0.01 0.00

[Acetyl]2 (enol)

296 340 356 399 400

19.1 10.4 39.5 100 24.9

1.10 1.26 0.88 0.38 0.81

302 346 362 405 406

16.7 10.1 38.7 100 23.2

0.82 0.65 0.16 0.05 0.31

Propionyl

298 314 315 371 372

22.5 65.2 14.9 100 23.8

1.06 0.96 1.07 0.93 0.99

304 320 321 377 378

19.0 57.5 12.2 100 22.7

0.00 0.00 0.00 0.00 0.00

TMS

387 388

100 29.7

0.24 0.48

393 394

100 27.6

0.05 0.26

[TMS]2 (enol)

444 459 460

24.4 100 36.8

1.64 1.48 1.94

450 465 466

20.9 100 36.0

0.38 0.13 0.55

t-BDMS

372

100

—

378

100

—

[t-BDMS]2 (enol)

486 487 543

78.8 63.7 7.65

0.00 0.00 0.00

492 493 549

85.7 29.3 7.05

0.00 0.00 0.00

Methoxyimino

287 313 344 345

9.12 12.9 100 20.3

2.47 0.66 3.57 1.07

290 319 350 351

10.4 13.0 100 21.0

0.60 0.00 0.12 1.75


230 295 343 400 401

78.1 19.4 53.7 100 29.4

0.00 0.00 0.00 0.00 0.00

236 301 349 406 407

53.6 22.3 12.1 100 16.1

0.00 0.00 0.00 0.00 0.00

Methoxyimino/ TMS

326 401 416 417

6.00 15.2 100 29.9

4.25 0.00 0.00 0.00

332 407 422 423

6.17 14.0 100 29.3

3.23 0.03 0.07 0.06

Hydroxylimino/ [propionyl]2

139 230 295 328 442

100 45.0 50.0 30.3 21.5

0.00 0.00 0.00 0.00 0.00

142 236 301 334 448

100 29.3 71.5 28.1 36.9

0.00 0.00 0.00 0.00 0.00


385 459 474 475

11.0 19.4 82.6 32.3

0.39 0.00 0.00 0.49

391 465 480 481

7.91 16.4 65.8 26.7

0.35 0.00 0.00 0.00

Hydroxylimino/ ethyl/propionyl

230 357 414 415

42.4 10.7 100 20.2

0.00 0.00 0.00 0.00

236 363 420 421

53.1 54.7 100 32.1

3.38 0.00 0.00 0.00

a–d




429

Table II-11. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Noroxycodone/noroxycodone-d3 CD Groupc

Noroxycodone Ion (m/z)d Rel. int. Analog’s cont.

Noroxycodone-d3 Ion (m/z)d Rel. int. Analog’s cont.

None

301

100

—

304

100

—

[Acetyl]2

239

70.3

—

242

55.7

—

[TFA]3 (enol)

336 362 475 589

37.9 33.1 12.0 39.3

— 3.28 0.41 0.32

339 365 478 592

33.5 29.3 10.9 33.6

— 1.39 3.32 0.70

Propionyl

301 357 358

17.8 100 22.5

2.84 1.59 2.79

304 360 361

17.8 100 22.1

0.52 0.42 0.31

[PFP]2

239 430 593

100 6.99 20.1

1.12 1.15 0.87

242 433 596

100 7.25 20.2

2.31 0.14 0.21

[HFB]2

239 449 480 693

100 3.78 6.00 11.1

3.54 4.82 4.42 3.29

242 452 483 696

100 3.59 6.56 12.2

2.38 2.68 0.91 1.21

[TMS]2

445

73.3

—

448

76.9

—

[TMS]3 (enol)

445 446 517 518

35.8 16.6 16.4 8.69

1.56 3.28 0.64 2.50

448 449 520 521

32.1 12.3 15.9 7.47

2.67 1.39 4.41 2.40

Methoxyimino/ ethyl

343 358

51.9 100

4.97 1.50

346 361

46.0 100

0.08 0.08


299 341 354 372

100 36.1 6.58 98.1

1.71 1.59 2.02 0.66

302 344 357 375

100 35.5 8.42 95.3

0.32 0.44 3.58 0.39

Methoxyimino/ [TFA]2

268 377 409 522

20.9 16.5 4.91 14.0

0.00 0.00 0.00 0.00

271 380 412 525

23.3 10.7 4.96 16.6

0.00 0.00 0.00 0.00


299 355 386

100 20.0 58.0

1.28 1.04 0.72

302 358 389

100 20.9 65.3

0.30 0.68 0.41

Methoxyimino/ PFP

476

24.4

0.00

479

25.5

0.00

Methoxyimino/ [HFB]2

477 509 691 722

15.4 5.53 2.23 8.51

0.97 0.44 0.00 0.69

480 512 694 725

17.1 5.65 2.71 10.1

1.59 2.35 1.33 0.59

Methoxyimino/ [TMS]2

359 474 475

29.2 100 38.2

2.63 0.36 1.04

362 477 478

27.9 100 36.9

1.57 3.15 1.28


283 357 387

9.48 6.27 30.7

0.00 0.00 0.00

286 360 390

10.7 14.6 30.7

0.00 0.00 0.00

Methoxyimino/ ethyl/propionyl

244 357 414

36.0 41.8 100

3.92 4.77 0.42

247 360 417

31.7 40.9 100

0.00 0.00 1.06

Methoxyimino/ ethyl/TMS

359 430

16.2 100

4.84 0.41

362 433

15.5 100

1.95 1.46



430


Noroxycodone Ion (m/z)d Rel. int. Analog’s cont.

Noroxycodone-d3 Ion (m/z)d Rel. int. Analog’s cont.

Methoxyimino/ ethyl/t-BDMS

342 343

100 22.1

1.02 1.26

345 346

100 22.0

0.53 0.00

Methoxyimino/ acetyl/TMS

371 413 444

36.2 44.8 32.2

0.00 0.00 0.00

373 416 447

13.2 32.0 14.7

0.00 0.00 0.00

Methoxyimino/ propionyl/TMS

269 427 458

73.7 51.2 55.4

— 0.00 0.00

272 430 461

73.3 54.4 53.1

— 0.00 0.00

Hydroxylimino/ [ethyl]2/TMS

243 373 429 444 445

30.6 11.0 23.6 100 39.8

0.00 0.00 0.00 0.00 0.00

246 376 432 447 448

23.2 19.0 15.4 100 26.9

0.00 0.00 0.00 0.00 0.00

a–d


Table II-12. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Buprenorphine/buprenorphine-d4 CD Groupc

Buprenorphine Ion (m/z)d Rel. int. Analog’s cont.

Buprenorphine-d4 Ion (m/z)d Rel. int. Analog’s cont.

Methyl

366 392 424 434 448 481

8.99 100 32.4 5.32 9.02 6.09

2.88 0.19 1.89 0.03 0.89 0.39

370 396 428 438 452 485

10.8 100 37.8 8.70 8.15 8.02

0.10 0.01 0.01 0.60 0.02 0.03

Ethyl

380 394 406 438 448 495

7.91 15.3 100 37.2 5.75 6.58

3.22 2.21 1.15 2.08 1.82 1.26

384 398 410 442 452 499

10.3 15.6 100 34.8 6.04 7.06

3.72 3.09 1.12 1.22 3.60 3.08

Acetyl

394 408 420 421 452

12.1 21.1 100 27.9 58.5

2.37 1.37 0.40 0.76 2.61

398 412 424 425 456

13.1 20.9 100 27.6 59.8

0.64 0.71 0.33 0.41 0.10

TFA (MBTFA)

474 506 516 548

100 43.3 7.46 3.84

0.09 0.36 0.51 0.10

478 510 520 552

100 38.6 3.38 4.18

3.15 1.20 2.26 2.38

PFP

498 512 524 556

9.85 20.2 100 32.0

1.51 0.01 0.29 1.04

602 516 528 560

3.52 20.0 100 28.6

4.89 0.02 0.78 0.35

HFB

562 574 606 630 663

15.6 100 41.7 3.87 4.08

4.42 2.65 4.75 0.00 2.80

566 578 610 634 667

19.8 100 31.2 1.11 2.42

1.08 0.91 1.32 1.91 0.08



431


Buprenorphine Ion (m/z)d Rel. int. Analog’s cont.

Buprenorphine-d4 Ion (m/z)d Rel. int. Analog’s cont.

TMS (MSTFA)

424 438 450 482 492 506 524 539

9.86 13.3 100 32.6 15.6 25.2 8.46 6.68

2.24 3.27 0.48 1.48 0.18 0.03 4.78 0.08

428 442 454 486 496 510 528 543

10.2 13.1 100 33.0 16.3 23.6 7.29 6.20

3.23 4.65 1.26 0.91 1.48 1.47 1.11 0.69

[TMS]2

438 506 554 555 611

30.8 41.5 48.3 52.1 11.7

3.50 1.70 0.00 2.25 0.00

442 510 558 559 615

14.4 26.3 35.4 14.6 2.23

2.50 0.95 1.46 0.00 0.00

t-BDMS

492 493 506 524 581

100 38.2 34.5 39.4 5.09

0.33 0.99 0.60 2.05 0.00

496 497 510 528 585

100 36.8 34.3 37.7 4.93

0.47 0.00 1.33 0.00 0.00

a–d


Table II-13. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Norbuprenorphine/norbuprenorphine-d3 CD Groupc

Norbuprenorphine Ion (m/z)d Rel. int. Analog’s cont.

Norbuprenorphine-d3 Ion (m/z)d Rel. int. Analog’s cont.

[Methyl]2

384

72.5

4.38

387

51.2

1.37

[Ethyl]2

412 469

41.9 8.62

4.92 1.59

415 472

50.5 0.44

1.12 1.66

[Acetyl]2

422 440 441 482

10.6 100 27.6 2.65

2.66 1.20 1.79 0.07

425 443 444 485

9.53 100 26.6 1.85

1.84 0.68 0.23 0.90

[TFA]2 (MBTFA)

548 530

100 5.87

0.77 0.92

551 533

100 15.4

3.31 4.68

[PFP]2

648 630

54.1 9.19

2.63 0.59

651 633

91.3 6.80

0.24 0.00

[HFB]2

748 730

41.0 3.72

0.17 1.49

751 733

47.6 4.02

1.02 2.17

[TMS]2 (BSTFA)

500 557

37.8 6.43

4.34 4.82

503 560

27.8 5.01

3.97 4.30

[TMS]3

524

42.6

—

527

16.9

—

t-BDMS

452 470 527

41.8 59.4 3.10

1.71 1.45 0.00

455 473 530

41.3 60.8 2.79

2.36 2.09 0.00

a–d




432

Table II-14. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Fentanyl/fentanyl-d5 CD Groupc None

a–d

Fentanyl Ion (m/z)d Rel. int. Analog’s cont. 146 189 245

54.0 40.0 100

0.81 1.00 0.19

Fentanyl-d5 Ion (m/z)d Rel. int. Analog’s cont. 151 194 250

54.0 38.0 100

0.20 0.19 0.13


Table II-15. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Norfentanyl/norfentanyl-d5 CD Groupc

Norfentanyl Ion (m/z)d Rel. int. Analog’s cont.

Norfentanyl-d5 Ion (m/z)d Rel. int. Analog’s cont.

None

93 159 175 232

64.8 44.6 55.0 2.19

4.08 3.82 4.65 3.42

98 164 180 237

48.5 37.9 50.1 2.45

0.71 0.05 0.02 0.28

Acetyl

93 132 158 175 231 274

46.2 73.5 65.7 14.6 66.2 8.33

1.74 1.20 0.70 1.60 0.73 2.18

98 137 163 180 236 279

45.0 64.2 59.2 13.0 62.1 8.42

2.62 0.07 1.01 0.20 0.06 0.06

TCA

93 132 175 249 285 340

15.1 29.3 9.06 5.45 4.70 9.27

3.39 1.62 4.51 0.91 2.26 0.23

98 137 180 254 290 345

15.4 28.1 8.33 5.02 4.12 8.16

0.55 3.97 2.33 0.22 2.13 3.26

TFA

93 104 132 150 272 328

38.8 10.6 29.6 100 9.09 6.32

1.43 2.56 2.69 1.65 0.68 0.51

98 109 137 155 277 333

39.0 9.05 27.9 100 8.84 6.69

1.37 0.89 0.13 0.11 0.00 0.00

PFP

93 132 150 175 322 378

27.0 28.3 100 14.0 7.10 4.23

1.21 1.27 1.18 1.91 0.42 0.28

98 137 155 180 327 383

26.7 26.3 100 13.2 7.66 4.72

1.02 0.06 0.08 0.37 0.85 0.36

HFB

93 132 150 175 372 428

22.7 28.5 100 13.0 7.21 3.63

1.65 1.46 1.52 1.68 0.70 0.48

98 137 155 180 377 433

23.2 26.9 100 12.4 6.42 3.25

0.87 0.09 0.06 0.30 0.04 0.05

4-CB

93 132 150 175 437

20.0 28.1 100 11.9 6.46

2.13 2.08 2.11 1.93 0.76

98 137 155 180 442

20.8 26.7 100 11.3 5.28

1.07 0.25 0.08 0.51 0.02



433


Norfentanyl Ion (m/z)d Rel. int. Analog’s cont.

Norfentanyl-d5 Ion (m/z)d Rel. int. Analog’s cont.

TMS

206 231 247 289 304

22.5 13.9 49.9 21.4 9.92

1.46 0.87 0.52 0.54 3.54

211 236 252 294 309

19.8 13.0 46.3 20.0 8.83

0.18 0.15 0.08 0.10 0.27

t-BDMS

132 206 207 231 289 290

31.1 100 18.6 4.32 72.7 17.7

0.77 0.42 1.55 0.42 0.34 0.38

137 211 212 236 294 295

31.2 100 18.5 4.69 79.5 19.6

0.79 0.02 0.64 0.23 0.01 0.02

a–d


Table II-16a. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Methadone/methadone-d3 CD Groupc None

a–d

Methadone Ion (m/z)d Rel. int. Analog’s cont. 223 294 309

26.1 5.68 12.8

1.30 0.28 0.64

Methadone-d3 Ion (m/z)d Rel. int. Analog’s cont. 226 297 312

22.0 27.1 9.79

0.64 0.47 0.00


Table II-16b. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Methadone/methadone-d9 CD Groupc None

a–d

Methadone Ion (m/z)d Rel. int. Analog’s cont. 72 223 294 309

100 2.00 2.00 0.15

0.74 55.8 1.16 1.62

0.08b 0.48c 5.70 44.7 0.12 0.87 0.16 3.60

Methadone-d9 Ion (m/z)d Rel. int. Analog’s cont. 78 226 303 318

100 4.00 3.00 0.30

0.03 0.04 0.00 0.00

0.28b 0.37 0.00 0.00

0.05c 0.03 0.00 0.00


Table II-17. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — 2-ethylidine-1,5-dimethyl-3,3-diphenylpyrrolidine/2ethylidine-1,5-dimethyl-3,3-diphenylpyrrolidine-d3

CD Groupc None

a–d

2-ethylidine-1,5-dimethyl3,3-diphenylpyrrolidine Ion (m/z)d Rel. int. Analog’s cont. 276 277

100 99.6

1.18 2.09

See the corresponding footnotes in Table I-1a. Tanle II — Opioids


2-ethylidine-1,5-dimethyl3,3-diphenylpyrrolidine-d3 Ion (m/z)d Rel. int. Analog’s cont. 279 280

95.5 100

2.11 0.15

434

Table II-18a. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Propoxyphene/propoxyphene-d5 CD Groupc None a–d

Propoxyphene Ion (m/z)d Rel. int. Analog’s cont. 208 250

5.00 1.00

4.50 0.36

Propoxyphen-d5 Ion (m/z)d Rel. int. Analog’s cont. 213 255

3.00 1.00

0.24 0.25


Table II-18b. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Propoxyphene/propoxyphene-d7 CD Groupc None

a–d

Propoxyphene Ion (m/z)d Rel. int. Analog’s cont. 91 193 250

6.10 4.00 1.50

— 3.53 0.19

Propoxyphen-d7 Ion (m/z)d Rel. int. Analog’s cont. 98 200 257

3.76 1.91 1.55

— 3.06 0.00


Table II-18c. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Propoxyphene/propoxyphene-d11 CD Groupc None

a–d

Propoxyphene Ion (m/z)d Rel. int. Analog’s cont. 58 178 250

100 3.00 1.00

0.21 2.73 0.00

Propoxyphen-d11 Ion (m/z)d Rel. int. Analog’s cont. 64 183 261

100 0.14 1.22

0.14 0.12 1.04


Table II-19. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Norpropoxyphene/norpropoxyphene-d5 CD Groupc None

a–d

Norpropoxyphene Ion (m/z)d Rel. int. Analog’s cont. 178 220 234

6.00 9.00 65.0

3.19 3.20 0.86

Norpropoxyphen-d5 Ion (m/z)d Rel. int. Analog’s cont. 183 225 239

5.00 10.0 71.0

0.94 0.39 0.06


Table II-20. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Meperidine/meperidine-d4

CD Groupc None a–d

Meperidine Ion (m/z)d Rel. int. Analog’s cont. 71 247

100 52.6

— 3.64

Meperidine-d4 Ion (m/z)d Rel. int. Analog’s cont. 73 251

100 56.6



— 0.78

435

Table II-21. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Normeperidine/normeperidine-d4 CD Groupc

Normeperidine Ion (m/z)d Rel. int. Analog’s cont.

None

57

100

—

Ethyl

232 246 247 260 261

17.8 100 17.1 14.6 20.5

Propyl

202 218 246 247 275

Butyl

Normeperidine-d4 Ion (m/z)d Rel. int. Analog’s cont. 59

100

—

0.86 0.17 0.46 0.18 0.67

236 250 251 264 265

18.1 100 17.4 15.2 20.2

0.05 0.06 0.04 0.33 0.05

4.66 2.83 100 17.1 2.94

2.12 0.24 0.08 0.15 2.24

206 222 250 251 279

4.85 2.66 100 17.5 3.02

0.04 0.06 0.02 0.03 0.06

246 247 289

100 18.4 2.92

0.07 0.31 1.40

250 251 293

100 18.1 2.90

0.03 0.11 0.18

Acetyl

158 187 188 202 232 275

30.9 100 14.0 28.0 31.5 30.2

1.82 0.70 1.42 0.63 0.65 0.61

161 191 192 206 236 279

27.6 100 15.3 32.3 34.8 34.2

4.45 0.34 0.47 0.17 0.12 0.08

TCA

342 232 344

100 34.5 66.3

— 1.82 0.38

346 236 348

100 38.9 66.4

— 3.97 0.37

TFA

143 241 255 256 329

72.7 100 33.5 48.8 38.5

2.56 0.42 0.52 0.64 0.04

146 243 259 260 333

55.2 100 32.4 51.6 38.6

0.73 1.10 0.18 3.16 0.02

PFP

143 291 305 306 379

66.6 100 30.7 43.4 36.5

2.72 0.49 0.53 0.80 0.03

146 293 309 310 383

54.0 100 30.4 47.5 38.5

2.34 1.24 0.18 0.07 0.02

HFB

341 355 356 429

100 29.6 42.6 34.5

— 0.08 0.10 0.03

343 359 360 433

100 29.4 46.9 37.4

— 2.21 4.23 0.24

4-CB

143 395 410 438 483

44.2 100 29.8 9.85 31.6

4.21 1.38 1.45 0.49 0.49

146 397 414 442 487

40.2 100 33.5 9.66 28.5

1.80 2.46 0.04 0.05 0.05

TMS

276 304 305

68.9 82.8 82.0

0.13 0.13 0.13

280 308 309

64.1 74.8 75.1

0.21 0.82 0.25

t-BDMS

262 274 290 291

13.8 7.82 100 23.4

0.89 0.37 0.02 0.04

266 278 294 295

22.1 8.26 100 23.9

0.12 0.28 0.14 0.02

a–c

See the corresponding footnotes in Table II-1A.



437

Summary of Drugs, Isotopic Analogs, and Chemical Derivatization Groups Included in Table III (Hallucinogens) Compound

Isotopic analog


Table #

Cannabinol

d3

Methyl, ethyl, propyl, butyl, propionyl

III-1

Tetrahydrocannabinol

d3

Methyl, ethyl, propyl, butyl, TFA, propionyl, PFP, HFB, TMS, t-BDMS

III-2

THC-OH

d3

[Methyl]2, [ethyl]2, [propyl]2, [butyl]2, [TFA]2, propionyl, [PFP]2, [HFB]2, [TMS]2, [t-BDMS]2

III-3

THC-COOH

d3 , d9

[Methyl]2, [ethyl]2, [propyl]2, [butyl]2, propionyl, [TMS]2, [t-BDMS]2, methyl/TFA, PFPoxy/PFP, HFPoxy/HFB

III-4

Ketamine

d4

None, acetyl, TFA, HFB, PFB, TMS

III-5

Norketamine

d4

None, acetyl, TCA, TFA, PFP, HFB, 4-CB, PFB, TMS, TFA/t-BDMS, PFP/t-BDMS, HFB/t-BDMS

III-6

Phencyclidine

d5

Acetyl, TFA, HFB, PFB, TMS

III-7

LSD

d3

None, TMS

III-8

Mescaline

d9

Acetyl, TCA, TFA, PFP, HFB, 4-CB, [TMS]2, t-BDMS, TFA/TMS, TFA/t-BDMS, PFP/TMS, PFP/t-BDMS, HFB/TMS, HFB/t-BDMS

III-9

Psilocin

d10

None, acetyl, [acetyl]2, [TMS]2, t-BDMS, [t-BDMS]2

Table III — Hallucinogens


III-10

439

Appendix Two — Table III Cross-Contributions Between Ions Designating the Drugs and Their Isotopically Labeled Analogs in Various Derivatization Forms — Hallucinogens Table III-1. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Cannabinol/cannabinol-d3 ............................................................................................................................ 440 Table III-2. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Tetrahydrocannabinol/tetrahydrocannabinol-d3 ............................................................................. 440 Table III-3. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — THC-OH/THC-OH-d3 .................................................................................................................... 441 Table III-4a. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — THC-COOH/THC-COOH-d3 ......................................................................................................... 442 Table III-4b. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — THC-COOH/THC-COOH-d9 ......................................................................................................... 442 Table III-5. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Ketamine/ketamine-d4 .................................................................................................................... 444 Table III-6. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Norketamine/norketamine-d4 ......................................................................................................... 444 Table III-7. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Phencyclidine/phencyclidine-d5 ..................................................................................................... 446 Table III-8. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — LSD/LSD-d3 ................................................................................................................................... 446 Table III-9. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Mescaline/mescaline-d9 .................................................................................................................. 446 Table III-10. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Psilocin/psilocin-d10 ....................................................................................................................... 447



440

Table III-1. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Cannabinol/cannabinol-d3 CD Groupc

Cannabinol Ion (m/z)d Rel. int. Analog’s cont.

Cannabinol-d3 Ion (m/z)d Rel. int. Analog’s cont.

Methyl

309 310 324

100 23.6 12.9

0.33 4.70 0.40

312 313 327

100 24.0 13.0

0.52 0.30 13.3

Ethyl

323

100

0.30

326

100

0.75

Propyl

337

100

0.61

340

100

2.24

Butyl

351 366

100 12.0

0.51 0.65

354 369

100 12.0

0.61 2.10

Propionyl

295 351 352

100 93.1 23.4

2.24 2.09 10.3

298 354 355

100 90.2 23.2

0.21 0.45 0.18

a–d


Table III-2. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Tetrahydrocannabinol/tetrahydrocannabinol-d3 CD Groupc

Tetrahydrocannabinol Ion (m/z)d Rel. int. Analog’s cont.

Tetrahydrocannabinol-d3 Ion (m/z)d Rel. int. Analog’s cont.

Methyl

245 285 313 328

44.2 33.0 100 74.1

1.59 2.56 0.33 0.09

248 288 316 331

42.3 32.4 100 74.8

1.07 0.49 0.26 0.28

Ethyl

259 313 327 328 342

40.2 40.6 100 24.2 88.7

3.14 0.73 0.00 2.41 0.00

262 316 330 331 345

39.5 40.2 100 24.3 91.8

1.14 0.52 0.29 0.16 0.35

Propyl

313 341 356

72.5 100 95.0

1.68 0.77 0.69

316 344 359

69.7 100 95.4

0.33 0.39 0.39

Butyl

313 327 355 370

61.7 20.4 100 99.3

4.98 3.72 1.49 0.31

316 330 358 373

64.1 20.6 100 99.6

0.82 0.51 0.42 0.40

TFA

297 313 327 367 395 410

74.8 33.4 53.5 83.4 83.7 100

— 1.13 1.23 0.73 0.52 0.09

300 316 330 370 398 413

64.9 31.3 51.3 80.8 80.7 100

— 1.13 0.49 0.33 0.31 0.39

Propionyl

313 314 341 370

50.2 21.7 100 9.26

1.48 2.69 — 0.93

316 317 344 373

49.2 21.0 100 8.66

0.93 0.22 — 0.54

PFP

377 378 417 445 460

100 20.1 45.9 10.6 59.0

0.63 4.53 0.80 1.03 0.08

380 381 420 448 463

100 20.2 44.3 9.78 54.8

1.39 1.01 0.51 0.48 0.48



441

Table III-2. (Continued) CD Groupc

Tetrahydrocannabinol Ion (m/z)d Rel. int. Analog’s cont.

Tetrahydrocannabinol-d3 Ion (m/z)d Rel. int. Analog’s cont.

HFB

297 313 427 467 495 510

100 34.1 54.0 80.2 73.7 98.1

1.39 1.92 1.44 1.42 1.77 0.99

300 316 430 470 498 513

100 33.8 53.5 80.9 73.5 97.8

0.47 0.69 0.07 0.46 0.42 0.49

TMS

303 343 371 386 387

47.5 30.6 100 91.7 29.1

1.12 3.44 0.44 0.09 2.33

306 346 374 389 390

47.6 29.0 100 92.7 29.5

1.85 1.39 1.26 1.24 0.52

t-BDMS

345 371 413 428

18.4 100 30.4 53.3

2.86 2.88 0.87 0.43

348 374 416 431

18.1 100 30.5 54.7

2.15 1.74 1.61 1.66

a–d


Table III-3. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — THC-OH/THC-OH-d3 CD Groupc

THC-OH Ion (m/z)d Rel. int.

Analog’s cont.

THC-OH-d3 Ion (m/z)d Rel. int. Analog’s cont.

[Methyl]2

231 299 314

85.9 100 81.2

2.03 1.96 1.87

234 302 317

83.7 100 81.0

0.42 0.17 0.18

[Ethyl]2

377

100

—

340

100

—

[Propyl]2

351

100

—

354

100

—

[Butyl]2

365

100

—

368

100

—

[TFA]2

313 340 365 408 409 522

9.38 8.02 34.4 100 45.4 7.86

1.90 3.72 1.24 0.07 0.89 0.00

316 343 368 411 412 525

9.15 7.81 33.3 100 45.2 7.84

1.35 1.87 1.32 1.06 0.26 0.55

Propionyl

312 368 369

100 48.8 18.4

1.47 0.90 5.34

315 371 372

100 46.0 17.6

0.51 1.30 0.54

[PFP]2

363 415 458 459 622

9.41 33.5 100 47.8 5.45

1.09 1.71 0.11 0.69 0.00

366 418 461 462 625

9.04 31.6 100 46.7 5.36

1.26 1.28 1.19 0.34 0.77

[HFB]2

413 465 508 509 722

9.50 30.6 100 47.6 3.34

2.44 2.83 1.11 1.71 1.23

416 468 511 512 725

8.78 29.7 100 47.4 3.68

2.62 1.53 1.27 0.33 0.81

[TMS]2

371 459 474

100 3.77 5.03

0.58 2.68 0.62

374 462 477

100 3.86 5.27

1.40 3.74 3.91

[t-BDMS]2

413

100

1.26

416

100

1.55

aa–d




442

Table III-4a. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — THC-COOH/THC-COOH-d3 CD Groupc

THC-COOH Ion (m/z)d Rel. int. Analog’s cont.

THC-COOH-d3 Ion (m/z)d Rel. int. Analog’s cont.

[Methyl]2

313 341 357 372

100 8.54 64.4 33.9

— 2.19 0.64 0.33

316 344 360 375

100 7.89 62.1 32.5

— 1.14 0.40 0.44

[Ethyl]2

327 371 385 400

100 32.7 40.4 25.9

0.59 0.94 0.56 0.28

330 374 388 403

100 33.8 40.6 26.0

1.66 0.42 0.47 0.61

[Propyl]2

341 385 413

100 38.9 41.0

0.66 0.61 0.00

344 388 416

100 38.9 40.6

0.98 0.49 0.96

[Butyl]2

355 399 441 456

100 41.8 41.3 22.0

2.91 2.12 2.74 0.00

358 402 444 459

100 42.0 41.8 22.2

0.58 0.70 0.62 0.70

Propionyl

314 337 370

87.9 2.60 6.04

1.82 3.12 1.94

317 340 373

84.5 2.96 5.78

0.37 1.06 0.62

[TMS]2

371 473 488

100 36.3 22.3

0.97 0.91 0.80

374 476 491

100 37.2 23.3

1.58 3.31 3.35

[t-BDMS]2

413 515 516 557

95.5 100 43.3 29.8

1.55 2.00 7.80 1.47

416 518 519 560

96.5 100 42.4 29.8

2.67 3.73 2.00 4.71

Methyl/TFA

379 395 411 439 454

20.5 49.5 9.54 100 46.3

1.70 0.79 4.33 0.53 0.12

382 398 414 442 457

21.1 50.7 9.35 100 46.5

2.42 2.33 0.42 0.46 0.48

PFPoxy/PFP

445 459 489 579 607 622

69.8 100 32.5 23.3 82.5 71.6

1.44 0.95 1.14 1.71 0.95 0.19

448 462 492 582 610 625

68.0 100 32.6 22.8 82.5 72.2

1.24 0.59 0.63 0.58 0.55 0.62

HFPoxy/HFB

477 495 523 539 690

100 28.0 27.3 39.0 38.6

— 4.17 1.84 0.83 0.82

480 498 526 542 693

100 27.8 27.6 39.2 38.2

— 1.96 0.54 0.63 0.00

a–d


Table III-4b. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — THC-COOH/THC-COOH-d9 CD Groupc [Methyl]2

THC-COOH Ion (m/z)d Rel. int. Analog’s cont. 313 314 341 357 372

100 24.1 8.54 64.4 33.9

0.24 1.79 0.87 0.00 0.00

THC-COOH-d9 Ion (m/z)d Rel. int. Analog’s cont. 322 323 350 363 381

100 22.2 7.38 46.2 32.3



0.02 0.73 0.00 0.00 0.00

443

Table III-4b. (Continued) CD Groupc

THC-COOH Ion (m/z)d Rel. int. Analog’s cont.

THC-COOH-d9 Ion (m/z)d Rel. int. Analog’s cont.

[Ethyl]2

327 328 355 371 385 400

100 24.7 8.32 32.7 40.4 25.9

0.08 0.41 0.28 0.00 0.02 0.00

336 337 364 380 391 409

100 22.9 7.82 34.3 39.5 26.1

0.01 0.33 0.00 0.00 0.00 0.00

[Propyl]2

341 342 369 385 413 428

100 25.9 8.97 38.9 41.0 23.8

0.00 0.00 0.00 0.00 0.00 0.00

350 351 378 394 419 437

100 24.1 11.3 37.3 40.7 23.8

0.01 0.20 0.00 0.00 0.00 0.00

[Butyl]2

355 399 441 456

100 41.8 41.3 22.0

2.91 2.12 2.74 0.00

364 408 447 465

100 41.8 40.6 22.9

0.58 0.70 0.62 0.00

Propionyl

258 259 271 299 314

100 18.2 16.6 18.1 87.9

2.08 4.78 1.36 0.80 0.62

264 265 277 305 323

100 18.0 12.3 16.0 88.9

0.05 1.19 0.48 0.19 0.13

[TMS]2

371 473 488

100 36.3 22.3

4.58 2.70 4.05

380 479 497

100 27.8 24.0

0.05 0.09 0.00

[t-BDMS]2

413 515 516 557 572

95.5 100 43.3 29.8 36.1

1.47 1.24 1.96 1.17 1.18

422 524 525 563 581

94.6 100 40.7 22.1 36.8

0.13 0.00 0.00 0.00 0.00

Methyl/TFA

341 379 395 411 439 454

31.4 20.5 49.5 9.54 100 46.3

4.92 0.25 0.15 3.64 0.04 0.00

350 385 404 414 445 463

31.7 14.1 53.8 9.44 100 50.0

0.79 2.56 0.46 0.41 0.00 0.00

PFPoxy/PFP

445 459 473 489 579 607 622

69.8 100 38.7 32.5 23.3 82.5 71.6

0.81 0.66 0.51 2.25 0.36 0.06 0.00

454 468 482 498 582 613 631

68.5 100 36.0 31.3 21.1 80.8 70.1

0.48 0.27 0.98 4.27 0.40 0.00 0.00

HFPoxy/HFB

477 495 523 539 675 690

100 28.0 27.3 39.0 23.7 38.6

0.79 0.27 0.29 0.23 0.50 0.04

486 504 532 548 681 699

100 27.1 25.4 38.6 24.9 37.3

0.08 5.36 0.15 0.96 0.00 0.00

a–d




444

Table III-5. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Ketamine/ketamine-d4 CD Groupc

Ketamine Ion (m/z)d Rel. int.

Analog’s cont.

Ketamine-d4 Ion (m/z)d Rel. int. Analog’s cont.

None

138 180 209

13.0 100 24.0

1.28 0.75 1.19

142 184 213

15.0 100 32.0

3.61 0.66 0.18

Acetyl

180 208 216 251

83.2 100 100 9.43

0.45 0.36 0.46 1.04

184 212 220 255

71.3 100 91.9 9.04

1.64 0.60 0.73 0.59

TFA

236 262 270 298

40.3 43.4 74.2 21.0

0.21 2.62 0.93 0.50

240 266 274 302

44.9 47.7 85.8 22.8

3.62 1.32 1.25 0.04

HFB

152 236 328 362 364 370 398

59.4 46.3 7.79 41.5 12.5 44.9 5.80

— 0.18 0.75 0.14 0.44 0.32 0.38

156 240 332 366 368 374 402

67.0 53.8 10.7 47.9 14.5 48.9 6.02

— 3.11 0.49 1.06 0.84 1.62 0.53

PFB

152 326 360 362 368 369 396 403 431

57.0 5.91 80.6 26.4 88.5 19.2 8.93 9.76 2.81

2.38 2.38 0.77 1.64 0.92 1.42 1.14 3.13 3.16

156 330 364 366 372 373 400 407 435

56.2 5.54 78.6 26.3 85.8 18.2 8.74 9.05 2.88

1.29 2.40 0.64 0.21 0.22 1.31 0.33 1.32 0.89

TMS

152 294

41.9 8.63

2.32 3.42

156 298

41.1 8.21

0.40 3.67

a–d


Table III-6. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Norketamine/Norketamine-d4 CD Groupc

Norketamine Ion (m/z)d Rel. int. Analog’s cont.

Norketamine-d4 Ion (m/z)d Rel. int. Analog’s cont.

None

102 166 195

10.0 100 25.0

3.75 0.85 0.83

106 170 199

11.0 100 33.0

0.76 0.38 0.17

Acetyl

102 194 202 203 230 231

46.9 15.6 100 14.2 78.3 12.1

0.72 0.77 0.06 0.35 0.23 0.13

106 198 206 207 234 235

47.1 13.4 100 14.7 77.3 12.8

2.44 2.59 1.42 5.01 0.23 0.06

TCA

102 306

28.0 96.0

2.02 0.25

106 310

22.8 95.1

0.32 4.73

TFA

284 102 214 239 256 275

100 76.6 67.7 47.0 56.2 37.1

— 0.85 0.13 0.43 0.31 0.15

288 106 218 243 260 279

100 72.7 60.4 38.3 55.8 37.0

— 1.39 0.79 2.48 4.69 1.89



445


Norketamine Ion (m/z)d Rel. int. Analog’s cont.

Norketamine-d4 Ion (m/z)d Rel. int. Analog’s cont.

PFP

264 289 290 306 325 334

55.3 45.2 50.5 77.1 44.9 100

1.03 1.86 8.83 0.93 0.98 0.88

268 293 294 310 329 338

54.1 42.7 5.00 78.6 45.2 100

0.10 0.23 0.84 0.43 0.48 0.02

HFB

102 314 339 356 375 377 384

58.9 69.1 43.8 100 41.8 13.1 84.8

2.06 0.39 1.09 0.29 0.33 2.85 0.21

106 318 343 360 379 381 388

57.1 69.8 41.0 100 40.8 12.8 90.8

0.52 0.09 0.35 0.26 0.54 0.10 0.03

4-CB

410 411 429 438

100 21.2 20.2 57.1

0.49 0.59 0.53 0.43

414 415 433 442

100 21.9 22.0 57.3

0.16 0.31 1.28 0.04

PFB

102 312 346 354 355 382

16.9 12.3 13.5 98.5 19.7 66.5

2.12 1.31 3.11 0.49 1.35 0.43

106 316 350 358 359 386

16.2 11.3 12.5 95.1 18.6 62.5

1.16 1.33 1.06 0.06 0.35 0.02

TMS

210 224 238 239 267 280

31.4 29.7 100 17.9 11.9 11.3

2.10 2.26 0.64 1.79 0.63 0.38

214 229 242 243 271 284

32.5 33.6 100 25.5 15.4 10.1

2.24 1.30 1.46 0.72 1.83 1.36

TFA/t-BDMS

336 376 378

25.8 100 38.3

0.71 0.29 0.46

340 380 382

26.4 100 37.8

3.69 2.18 0.17

PFP/t-BDMS

263 296 309 324 358 426 428

62.6 51.0 35.8 35.4 20.6 100 37.9

1.58 2.25 5.85 2.89 1.75 0.04 0.41

267 300 313 328 362 430 432

55.0 51.2 28.2 34.3 19.8 100 38.4

3.83 10.7 2.74 4.44 4.41 2.41 0.19

HFB/t-BDMS

263 359 374 476 478

44.4 27.7 35.3 100 38.8

0.75 2.83 0.62 0.03 0.51

267 363 378 480 482

57.2 25.9 40.4 100 38.5

2.52 3.78 4.61 2.16 0.12

a–d




446

Table III-7. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Phencyclidine/phencyclidine-d5 CD Groupc None

a–d

Phencyclidine Ion (m/z)d Rel. int. Analog’s cont. 91 186 200 242

30.0 22.0 100 35.0

0.53 0.16 0.03 0.02

Phencyclidine-d5 Ion (m/z)d Rel. int. Analog’s cont. 96 190 205 246

28.0 15.0 100 28.0

1.01 0.00 0.02 0.10


Table III-8. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — LSD/LSD-d3 CD Groupc

LSD Ion (m/z)d Rel. int.

Analog’s cont.

LSD-d3 Ion (m/z)d Rel. int.

Analog’s cont.

None

221 323

100 99.3

1.48 0.62

224 326

93.0 100

4.11 0.23

TMS

293 395 396

81.1 93.8 29.0

— 0.69 4.04

296 398 399

78.2 90.0 27.8

— 1.56 1.11

a–d


Table III-9. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Mescaline/mescaline-d9 CD Groupc

Mescaline Ion (m/z)d Rel. int. Analog’s cont.

Mescaline-d9 Ion (m/z)d Rel. int. Analog’s cont.

Acetyl

179 181 194 195 253

47.1 47.9 100 13.0 16.3

1.17 1.29 1.13 1.32 1.14

185 190 203 204 262

46.8 48.0 100 10.5 16.2

0.07 0.15 0.01 0.14 0.03

TCA

179 181 194 195 355 357

34.5 100 97.4 20.8 17.6 17.1

0.52 0.46 0.23 1.04 0.11 0.05

185 190 203 204 364 366

32.5 100 98.8 19.1 22.5 21.9

0.34 0.29 0.05 1.05 0.00 0.02

TFA

179 181 194 307

22.2 100 35.3 34.8

0.36 0.47 0.38 0.25

185 190 203 316

22.0 100 34.4 37.9

0.06 0.06 0.06 0.00

PFP

179 181 194 357

25.4 100 38.6 38.8

0.20 0.33 0.21 0.11

185 190 203 366

25.6 100 38.1 40.2

0.12 0.16 0.02 0.00

HFB

179 181 194 407

27.3 100 42.5 39.2

0.35 0.28 0.21 0.07

185 190 203 416

27.1 100 41.3 39.5

0.08 0.08 0.03 0.00



447


Mescaline Ion (m/z)d Rel. int. Analog’s cont.

Mescaline-d9 Ion (m/z)d Rel. int. Analog’s cont.

4-CB

179 181 194 416 461

40.2 100 94.8 4.00 27.8

0.70 0.92 0.75 0.74 0.37

185 190 203 425 470

36.2 100 92.3 4.40 31.4

0.15 0.12 0.04 0.35 0.00

[TMS]2

266 340 354

1.06 9.19 0.24

1.96 0.04 1.65

275 349 363

1.05 11.0 0.29

0.08 0.00 0.60

t-BDMS

181 268 269 310

8.06 37.1 7.46 3.03

4.93 0.50 1.06 0.33

190 277 278 319

8.65 38.0 6.66 3.04

2.69 0.05 0.42 0.08

TFA/TMS

181 182 194 379 380

100 12.4 4.45 24.1 5.76

0.49 1.38 2.64 0.25 0.34

190 191 203 388 389

100 9.76 4.47 26.0 5.49

0.14 0.66 0.50 0.01 0.06

TFA/t-BDMS

181 182 195 220 421

100 13.1 24.0 13.5 22.4

0.26 2.46 0.83 0.46 0.01

190 191 204 229 430

100 10.0 24.6 14.9 27.6

0.27 1.61 0.70 0.39 0.02

PFP/TMS

181 182 195 429 430

100 12.9 8.14 30.3 7.57

0.43 0.95 0.88 0.15 0.15

190 191 204 438 439

100 10.5 8.71 30.2 6.72

0.27 0.96 1.23 0.02 0.03

PFP/t-BDMS

181 195 414 471

100 33.6 4.69 26.3

0.25 0.34 0.04 0.02

190 204 423 480

100 33.1 3.42 19.6

0.32 0.46 0.05 0.01

HFB/TMS

181 182 195 479 480

100 11.8 8.00 24.3 6.20

0.33 0.98 2.81 0.17 0.17

190 191 204 488 489

100 9.42 7.98 21.2 4.80

0.08 2.92 1.17 0.00 0.10

HFB/t-BDMS

181 195 521

100 28.6 22.4

0.34 0.32 0.04

190 204 530

100 28.6 17.0

0.25 0.76 0.23

a–d


Table III-10. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Psilocin/psilocin-d10 CD Groupc None

Psilocin Ion (m/z)d Rel. int. 58 59 204 205

100 3.93 22.4 3.12

Analog’s cont. 1.45 2.30 1.21 1.54

Psilocin-d10 Ion (m/z)d Rel. int. 66 67 214 215



100 4.17 21.6 3.30

Analog’s cont. 0.25 2.55 0.09 0.24

448


Psilocin Ion (m/z)d Rel. int.

Analog’s cont.

Psilocin-d10 Ion (m/z)d Rel. int.

Analog’s cont.

Acetyl

58 59 146 160 246

100 4.02 4.87 2.36 3.74

0.26 0.05 3.13 3.64 0.21

66 67 148 165 256

100 3.87 2.47 1.08 3.11

0.10 1.25 2.00 0.42 0.02

[Acetyl]2

58 59 146 160 288

100 3.76 3.67 2.09 0.58

0.22 0.96 3.52 3.92 2.70

66 67 148 165 298

100 3.78 2.11 0.91 0.46

0.08 1.73 2.34 0.85 1.47

[TMS]2

58 290 333 348 349

56.7 100 4.97 28.2 8.84

0.38 — 0.11 0.04 0.05

66 292 343 358 359

64.3 100 6.22 32.3 10.1

0.03 — 0.50 0.01 0.05

t-BDMS

58 303 318 319

100 1.28 16.2 4.23

0.52 0.36 0.18 0.23

66 313 328 329

100 1.43 15.8 4.23

0.06 4.48 0.15 0.33

[t-BDMS]2

58 432 433

100 11.1 4.27

0.60 0.16 0.00

66 442 443

100 11.7 4.42

0.01 0.00 0.87

a–d




449

Summary of Drugs, Isotopic Analogs, and Chemical Derivatization Groups Included in Table IV (Depressant/Hypnotics) Compound

Isotopic analog


Table #

Pentobarbital

d5

None, [methyl]2, [ethyl]2, [propyl]2, [butyl]2, [TMS]2, [t-BDMS]2

IV-1

Phenobarbital

d5, d5 (ring)

[Methyl]2, [ethyl]2, [propyl]2, [butyl]2, [TMS]2, [t-BDMS]2

IV-2

d5 ,

13C

4


IV-3

Sceobarbital

d5 ,

13C

4


IV-4

Methohexital

d5

Butalbital

None, methyl, ethyl, propyl, butyl, TMS, t-BDMS

IV-5

γ-Hydroxybutyric acid d6

[TMS]2, [t-BDMS]2

IV-6

γ-Butyrolactone

None

IV-7

d6

Table IV — Depressants/Hypnotics


451

Appendix Two — Table IV Cross-Contributions Between ions Designating the Drugs and Their Isotopically Labeled Analogs in Various Derivatization Forms — Depressants/Hypnotics Table IV-1. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Pentobarbital/pentobarbital-d5 ....................................................................................................... 452 Table IV-2a. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Phenobarbital/phenobarbital-d5 ...................................................................................................... 452 Table IV-2b. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Phenobarbital/phenobarbital-d5 (ring) ........................................................................................... 453 Table IV-3a. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Butalbital/butalbital-d5 ................................................................................................................... 453 Table IV-3b. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Butalbital/butalbital-13C4 ................................................................................................................. 454 Table IV-4a. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Secobarbital/secobarbital-d5 ........................................................................................................... 455 Table IV-4b. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Secobarbital/secobarbital-13C4 ....................................................................................................... 455 Table IV-5. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Methohexital/methohexital-d5 ........................................................................................................ 456 Table IV-6. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — γ-Hydroxybutyric acid/γ-Hydroxybutyric acid-d6 ................................................................................ 457 Table IV-7. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — γ-Butyrolactone/γ-butyrolactone-d6 .................................................................................................... 457



452

Table IV-1. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Pentobarbital/pentobarbital-d5 CD Groupc

Pentobarbital Ion (m/z)d Rel. int. Analog’s cont.

Pentobarbital-d5 Ion (m/z)d Rel. int. Analog’s cont.

None

156 157

100 21.6

2.83 3.35

161 162

100 23.3

1.41 1.60

[Methyl]2

184

82.5

4.73

189

100

0.00

[Ethyl]2

184 197 212 213

5.63 100 93.0 12.5

1.59 1.62 3.39 4.18

189 199 217 218

6.29 76.5 100 13.2

0.01 1.35 0.00 0.00

[Propyl]2

97 156 181 198 225 240

24.6 51.9 15.0 83.5 23.4 100

3.74 0.63 1.86 0.65 3.41 4.56

102 161 186 203 227 245

23.9 53.5 16.9 83.9 18.9 100

0.02 0.01 0.14 0.01 1.75 0.00

[Butyl]2

97 156 195 251

26.2 29.4 70.1 100

2.66 4.10 0.52 0.22

102 161 200 256

25.4 27.9 67.0 100

0.45 0.52 0.07 0.27

[TMS]2

169 184

100 82.5

3.25 2.97

171 189

90.4 100

0.94 0.00

[t-BDMS]2

327

74.4

—

332

73.5

—

a–d


Table IV-2a. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Phenobarbital/phenobarbital-d5 CD Groupc

Phenobarbital Ion (m/z)d Rel. int. Analog’s cont.

Phenobarbital-d5 Ion (m/z)d Rel. int. Analog’s cont.

[Methyl]2

232 260

100 2.67

— 0.09

233 265

100 4.28

— 0.00

[Ethyl]2

146 260 288

49.9 100 1.60

4.20 — 0.07

151 261 293

58.0 100 2.22

0.03 — 0.05

[Propyl]2

146 189 275

87.1 12.5 13.0

2.49 1.73 1.54

151 194 280

100 14.6 16.8

0.05 0.41 0.55

[Butyl]2

146 189 289 344

27.8 9.10 43.0 2.98

3.13 3.73 0.77 0.11

151 194 294 349

26.5 7.38 37.2 2.55

0.08 0.39 0.02 0.06

[TMS]2

146

100

—

151

100

—

[t-BDMS]2

403

100

—

408

100

—

a–d




453

Table IV-2b. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Phenobarbital/phenobarbital-d5(ring) CD Groupc

Phenobarbital Ion (m/z)d Rel. int. Analog’s cont.

Phenobarbital-d5(ring) Ion (m/z)d Rel. int. Analog’s cont.

[Methyl]2

117 146 175 188 232 260

23.6 17.8 18.6 9.82 100 2.67

1.24 0.52 0.35 0.26 0.04 0.05

122 151 180 193 237 265

17.4 16.4 18.4 9.97 100 2.38

0.12 0.02 0.02 0.02 0.01 0.04

[Ethyl]2

103 117 146 202 232 260

11.3 31.8 49.9 9.28 17.4 100

0.92 1.79 1.85 0.50 0.47 0.04

108 122 151 207 237 265

10.8 23.9 47.8 8.84 16.1 100

0.22 0.09 0.03 0.09 0.06 0.00

[Propyl]2

117 146 204 246 275 288

42.5 87.1 23.3 40.3 13.0 100

1.09 0.64 0.35 0.04 1.29 0.02

122 151 209 251 280 293

35.5 91.3 26.8 39.5 12.8 100

0.08 0.06 1.00 0.73 0.62 0.03

[Butyl]2

117 146 260 289 299 316

52.3 100 17.0 73.4 29.0 5.97

1.07 0.69 0.62 0.24 0.11 0.06

122 151 265 294 304 321

41.1 100 17.0 71.5 28.5 66.7

0.27 0.10 0.53 0.04 0.50 0.06

[TMS]2

146

100

—

151

100

—

[t-BDMS]2

403

100

—

408

100

—

a–d


Table IV-3a. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Butalbital/butalbital-d5 CD Groupc

Butalbital Ion (m/z)d Rel. int. Analog’s cont.

Butalbital-d5 Ion (m/z)d Rel. int. Analog’s cont.

None

168

100

—

173

100

—

[Methyl]2

181 196 237

26.8 100 2.42

4.46 1.09 1.54

184 201 242

17.9 100 2.76

0.22 0.00 0.00

[Ethyl]2

209 223 224 265

15.1 59.7 100 3.81

3.86 4.16 0.65 0.53

212 228 229 270

15.1 63.3 100 3.86

0.77 0.01 0.00 0.00

[Propyl]2

210 251 252 293

58.4 81.2 100 7.08

1.11 1.84 0.61 0.48

215 256 257 298

64.8 63.7 100 8.05

0.03 0.02 0.00 0.00

[Butyl]2

224 263 279 280 293

22.5 100 64.0 47.6 24.0

4.77 0.16 1.41 1.28 3.61

229 268 284 285 298

21.9 100 40.1 40.2 25.0

0.46 0.02 0.06 0.01 0.08

[TMS]2

353

100

—

358

100

—



454

Table IV-3a. (Continued) CD Groupc [t-BDMS]2 a–d

Butalbital Ion (m/z)d Rel. int. Analog’s cont. 395

100

—

Butalbital-d5 Ion (m/z)d Rel. int. Analog’s cont. 400

100

—


Table IV-3b. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Butalbital/butalbital-13C4 Butalbital CD Group

c

Ion

(m/z)d

Rel. int.

Analog’s cont.

Ion

(m/z)d

Butalbital-13C4 Rel. int.

Analog’s cont.

None

168

100

—

172

100

—

[Methyl]2

138 169 181 195 196 209

17.5 14.0 27.8 71.2 100 15.9

2.01 2.15 0.39 0.35 0.16 0.50

141 173 185 199 200 213

20.1 14.3 28.6 76.5 100 16.1

2.79 0.07 0.02 0.11 0.01 0.35

[Ethyl]2

196 209 223 224 237 265

15.7 15.1 59.7 100 12.9 3.81

1.48 1.37 1.29 0.88 1.50 1.40

200 213 227 228 241 269

16.1 15.1 63.3 100 13.2 3.86

0.10 0.14 0.17 0.01 0.57 0.00

[Propyl]2

210 251 252 265 293

60.1 86.4 100 22.1 6.27

0.82 0.77 0.55 1.91 1.01

214 255 256 269 297

61.0 90.7 100 22.4 6.43

0.25 0.15 0.01 0.79 0.04

[Butyl]2

224 263 279 280 293

21.7 100 69.1 48.2 24.4

2.67 0.46 1.09 0.74 0.72

228 267 283 284 297

21.7 100 70.5 46.0 24.4

1.54 0.19 0.27 0.04 0.97

[TMS]2

269 297 312 325 353 354

13.5 23.5 43.9 30.6 100 29.5

4.78 2.50 2.22 2.06 2.12 2.18

273 301 316 329 357 358

13.4 23.3 42.9 30.3 100 26.1

1.51 0.60 0.67 3.13 0.65 0.44

[t-BDMS]2

297 395 396 397 437

12.5 100 39.4 15.6 11.4

1.29 1.23 1.56 3.64 0.80

301 399 400 401 441

11.9 100 34.1 26.6 11.0

0.37 0.52 0.38 0.62 0.61

a–d




455

Table IV-4a. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Secobarbital/secobarbital-d5 Secobarbital CD Groupc

Ion (m/z)d Rel. int.

Secobarbital-d5

Analog’s cont.


Analog’s cont.

None

168

100

3.78

173

100

1.93

[Methyl]2

138 196

18.0 100

4.77 1.55

143 201

13.2 100

3.05 0.00

[Ethyl]2

196 224

15.3 100

4.54 1.63

201 229

16.7 100

0.41 0.36

[Propyl]2

210 252 322

50.1 100 5.35

1.40 2.37 0.26

215 257 327

54.9 100 6.87

0.07 0.03 0.55

[Butyl]2

224 263 279 350

26.1 84.4 100 7.39

4.77 0.40 — 0.14

229 268 284 355

29.1 100 63.2 9.29

0.09 2.14 — 0.65

[TMS]2

297 312 339 367

100 54.0 50.3 61.6

— 4.64 4.17 3.78

302 317 344 372

100 60.4 62.5 78.0

— 0.06 0.36 0.29

[t-BDMS]2

339

49.5

—

344

47.8

—

a–d


Table IV-4b. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Secobarbital/secobarbital-13C4 Secobarbital CD Group

c

Ion

(m/z)d

Rel. int.

Analog’s cont.

Ion

(m/z)d

Secobarbital-13C4 Rel. int.

Analog’s cont.

None

168

100

—

172

100

—

[Methyl]2

138 181 195 196

19.1 42.1 74.8 100

3.10 1.79 0.50 0.55

141 185 199 200

20.9 44.1 81.1 100

2.26 0.17 0.12 0.01

[Ethyl]2

196 209 223 224

14.1 21.0 67.4 100

2.12 0.59 0.41 0.48

200 213 227 228

14.1 21.8 72.1 100

0.11 0.23 0.16 0.01

[Propyl]2

210 237 251 252

48.5 11.5 94.0 100

1.06 1.85 0.48 0.58

214 241 255 256

48.9 12.0 98.9 100

0.20 0.79 0.15 0.01

[Butyl]2

168 224 279 280

23.1 24.1 100 84.5

4.01 2.74 0.56 0.65

172 228 283 284

22.2 23.5 100 79.4

0.17 0.34 0.68 0.15

[TMS]2

297 311 312 339 367

100 30.4 58.8 53.9 64.5

1.48 1.47 1.25 1.39 1.12

301 315 316 343 371

100 32.4 58.1 53.7 64.7

0.68 3.67 0.47 2.32 0.78



456

Table IV-4b. (Continued) CD Groupc [t-BDMS]2

a–d

Secobarbital Ion (m/z)d Rel. int. Analog’s cont. 281 339 381 409 410 451

9.33 53.4 4.82 100 36.1 8.81

2.00 1.07 0.97 1.06 1.26 0.85

Secobarbital-13C3 Ion (m/z)d Rel. int. Analog’s cont. 285 343 385 413 414 455

9.13 52.3 4.65 100 32.5 8.54

0.86 0.45 0.98 0.53 0.53 4.85


Table IV-5. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Methohexital/methohexital-d5 Methohexital CD Groupc


Methohexital-d5

Analog’s cont.


Analog’s cont.

None

233 247 261

51.8 52.4 15.0

1.20 0.43 0.15

238 252 266

31.7 41.1 9.01

0.08 0.09 0.00

Methyl

247 261 275

42.1 46.0 15.6

3.48 0.55 0.04

252 266 280

21.3 34.4 8.84

0.31 0.30 0.51

Ethyl

209 275 289

38.5 39.4 14.8

— 0.86 0.00

214 280 294

20.9 27.8 7.51

— 0.02 0.10

Propyl

223 289 303

40.7 39.2 14.4

— 0.86 0.18

228 294 308

20.8 29.2 7.55

— 0.02 0.29

Butyl

237 303 318

39.0 39.9 15.3

— 2.02 0.50

242 308 323

19.6 30.7 13.6

— 0.17 0.35

TMS

239 305 319 333

100 13.6 38.7 7.56

2.33 3.91 0.17 0.20

244 310 324 338

100 10.5 39.1 4.59

0.11 0.10 0.01 0.23

t-BDMS

239 240 319

100 18.5 52.2

0.62 2.26 0.51

244 245 324

100 18.1 51.6

0.04 0.39 0.04

a–d




457

Table IV-6. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — γ-Hydroxybutyric acid/γ-hydroxybutyric acid-d6 CD Groupc

γ-Hydroxybutyric acid Ion (m/z)d Rel. int. Analog’s cont.

γ-Hydroxybutyric acid-d6 Ion (m/z)d Rel. int. Analog’s cont.

[TMS]2

233 234 235

27.9 5.55 2.52

1.49 1.60 2.71

239 240 241

29.9 6.12 2.84

0.75 0.79 0.84

[t-BDMS]2

275 276 277 317

76.6 18.7 7.78 3.00

0.06 0.08 0.37 0.09

281 282 283 323

100 24.4 10.1 4.39

0.01 0.01 0.03 0.27

a–d


Table IV-7. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — γ-Butyrolactone/γ-butyrolactone-d6 CD Groupc None

a–d

γ-Butyrolactone Ion (m/z)d Rel. int. Analog’s cont. 42 56 86

100 36.2 85.7

— 0.73 0.16

γ-Butyrolactone-d6 Ion (m/z)d Rel. int. Analog’s cont. 48 60 92




100 32.4 65.6

— 0.00 0.00

459

Summary of Drugs, Isotopic Analogs, and Chemical Derivatization Groups Included in Table V (Antianxiety Agents) Compound

Isotopic analog


Table #

Oxazepam

d5

None, [Methyl]2, [ethyl]2, [propyl]2, [butyl]2, [TMS]2, [t-BDMS]2

V-1

Diazepam

d 3, d 5

None

V-2

Nordiazepam

d5

None, methyl, ethyl, propyl, butyl, TMS, t-BDMS

V-3

Nitrazepam

d5

Methyl, ethyl, propyl, butyl, TMS, t-BDMS

V-4

Temazepam

d5

None, methyl, ethyl, propyl, butyl, acetyl, TMS, t-BDMS

V-5

Clonazepam

d4

Methyl, ethyl, propyl, butyl, TMS, t-BDMS

V-6

7-Aminoclonazepam

d4

[Methyl]3, [ethyl]2, [ethyl]3, propyl, [propyl]2, butyl, [butyl]2, PFP, HFB, [TMS]2, t-BDMS, [t-BDMS]2 TFA/[TMS]2, TFA/[t-BDMS]2, [TFA]2/t-BDMS, PFP/TMS, PFP/[TMS]2, PFP/[t-BDMS]2, HFB/[t-BDMS]2

V-7

Prazepam

d5

None

V-8

Lorazepam

d4

[Methyl]2, [ethyl]2, [propyl]2, [butyl]2, HFB, [TMS]2, [t-BDMS]2

V-9

Flunitrazepam

d 3, d 7

None

V-10

7-Aminoflunitrazepam

d 3, d 7

None, [methyl]2, ethyl, [ethyl]2, propyl, butyl, acetyl, TFA, PFP, HFB, TMS, TFA/TMS, TFA/t-BDMS, PFP/TMS, PFP/t-BDMS, HFB/TMS, HFB/t-BDMS

V-11

N-Desalkylflurazepam

d4

None, methyl, [methyl]2, ethyl, propyl, butyl, acetyl, TMS, t-BDMS

V-12

N-Desmethylflunitrazepam d4

[Methyl]2, ethyl, propyl, butyl, acetyl, TMS, t-BDMS

V-13

2-Hydroxyethylflurazepam d4

None, butyl, TMS, t-BDMS

V-14

Estazolam

d5

None

V-15

Alprazolam

d5

None

V-16

α-Hydroxyalprazolam

d5

TMS, t-BDMS

V-17

α-Hydroxytriazolam

d4

TMS, t-BDMS

V-18

Mianserin

d3

None

V-19

Methaqualone

d7

None

V-20

Haloperidol

d4

TMS

V-21

Table V — Antianxiety Agents


461

Appendix Two — Table V Cross-Contributions Between Ions Designating the Drugs and Their Isotopically Labeled Analogs in Various Derivatization Forms — Antianxiety Agents Table V-1. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Oxazepam/oxazepam-d5 ................................................................................................................. 463 Table V-2a. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Diazepam/diazepam-d3 ................................................................................................................... 463 Table V-2b. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Diazepam/diazepam-d5 ................................................................................................................... 464 Table V-3. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Nordiazepam/nordiazepam-d5 ........................................................................................................ 464 Table V-4. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Nitrazepam/nitrazepam-d5 .............................................................................................................. 465 Table V-5. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Temazepam/temazepam-d5 ............................................................................................................. 465 Table V-6. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Clonazepam/clonazepam-d4 ........................................................................................................... 466 Table V-7. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — 7-Aminoclonazepam/7-aminoclonazepam-d4 ................................................................................ 467 Table V-8. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Prazepam/prazepam-d5 ................................................................................................................... 468 Table V-9. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Lorazepam/lorazepam-d4 ............................................................................................................... 469 Table V-10a. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Flunitrazepam/flunitrazepam-d3 ..................................................................................................... 469 Table V-10b. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Flunitrazepam/flunitrazepam-d7 ..................................................................................................... 469 Table V-11a. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — 7-Aminoflunitrazepam/7-Aminoflunitrazepam-d3 ........................................................................ 470 Table V-11b. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — 7-Aminoflunitrazepam/7-Aminoflunitrazepam-d7 ........................................................................ 471 Table V-12. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — N-Desalkylflurazepam/N-desalkylflurazepam-d4 .......................................................................... 472 Table V-13. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — N-Desmethylflunitrazepam/N-desmethylflunitrazepam-d4 ........................................................... 473 Table V-14. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — 2-Hydroxyethylflurazepam/2-hydroxyethylflurazepam-d4 ........................................................... 474 Table V-15. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Estazolam/estazolam-d5 ................................................................................................................. 474 Table V-16. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Alprazolam/alprazolam-d5 .............................................................................................................. 474 Table V-17. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — α-Hydroxyalprazolam/α-hydroxyalprazolam-d5 ........................................................................... 475 Table V-18. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — α-Hydroxytriazolam/α-hydroxytriazolam-d4 ................................................................................ 475 Table V-19. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Mianserin/mianserin-d3 .................................................................................................................. 475 Table V — Antianxiety Agents


462

Table V-20. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Methaqualone/methaqualone-d7 ..................................................................................................... 476 Table V-21. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Haloperidol/haloperidol-d4 ............................................................................................................. 476



463

Table V-1. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Oxazepam/oxazepam-d5 CD Groupc

Ion (m/z)

Oxazepam Rel. int. Analog’s cont.

Ion (m/z)

Oxazepam-d5 Rel. int. Analog’s cont.

None

205 241 269 270

69.1 71.4 100 74.0

4.24 4.36 3.04 4.29

210 246 274 275

68.6 81.2 100 93.0

0.21 0.22 0.30 0.20

[Methyl]2

255 256 271 273 314

48.7 32.6 100 32.4 24.5

0.47 0.83 0.51 4.67 0.37

260 261 276 278 319

43.2 31.6 100 35.1 24.8

1.19 0.16 0.04 0.34 0.06

[Ethyl]2

257 270 285 287 342

34.7 19.1 100 34.1 11.8

1.20 1.49 0.56 3.11 0.40

262 275 290 292 347

32.5 19.3 100 33.3 12.8

0.56 0.46 0.29 0.00 1.33

[Propyl]2

241 257 285 299 370

18.4 47.4 20.7 100 9.48

2.06 1.19 1.09 0.31 1.05

246 262 290 304 375

18.7 46.0 20.8 100 8.26

0.34 0.28 0.21 0.07 0.15

[Butyl]2

241 257 299 313 315 398

16.7 45.1 21.4 100 34.3 5.83

1.49 0.89 0.80 0.20 0.54 1.29

246 262 304 318 320 403

15.9 42.6 20.5 100 33.7 5.37

0.95 1.87 0.11 0.07 0.00 1.59

[TMS]2

313 340 401 415 429 430

26.0 12.4 14.9 15.1 100 54.7

1.54 0.84 3.75 0.22 — 0.15

318 345 406 420 433 435

42.9 19.2 31.8 22.8 100 86.9

0.35 2.03 0.40 0.57 — 0.40

[t-BDMS]2

313 457 458 459

19.6 100 36.8 45.6

3.02 1.44 1.52 1.57

318 462 463 464

20.7 100 37.7 45.6

1.73 1.02 0.55 0.09

a–d


Table V-2a. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Diazepam/diazepam-d3 CD Groupc None a–d

Ion (m/z) 256 257

Diazepam Rel. int. Analog’s cont. 100 44.8

— 3.11

Ion (m/z) 259 260




Diazepam-d3 Rel. int. Analog’s cont. 100 44.5

— 2.83

464

Table V-2b. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Diazepam/diazepam-d5 CD Groupc None

a–d

Ion (m/z) 256 258 283 285

Diazepam Rel. int. Analog’s cont. 100 36.3 91.3 40.7

0.36 1.69 0.09 1.25

Ion (m/z) 261 263 287 289

Diazepam-d5 Rel. int. Analog’s cont. 100 36.1 86.4 79.3

0.12 0.02 4.39 0.04


Table V-3. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Nordiazepam/nordiazepam-d5 CD Groupc

Ion (m/z)

Nordiazepam Rel. int. Analog’s cont.

Nordiazepam-d5 Ion (m/z) Rel. int. Analog’s cont.

None

241 242 270

88.0 100 68.8

4.06 3.74 3.23

246 247 275

77.2 100 73.0

1.91 0.16 0.05

Methyl

255 256 257 283 284

44.1 100 46.4 89.8 69.4

1.18 0.41 2.69 0.11 0.13

260 261 262 287 289

41.5 100 44.6 84.2 78.1

3.42 0.12 0.03 4.76 0.04

Ethyl

270 271 297 298

100 55.6 98.3 62.7

0.16 0.96 0.08 0.10

275 276 301 303

100 40.1 89.8 70.5

0.14 0.04 3.73 0.04

Propyl

269 270 284 311 312

90.3 59.4 81.9 100 58.7

0.16 0.35 0.15 0.09 0.11

273 275 289 315 317

82.9 70.2 84.2 100 71.7

3.14 0.11 0.14 3.01 0.03

Butyl

255 269

18.3 100

2.27 0.83

260 273

18.8 98.0

0.63 2.91

270 298 325 326

57.1 60.8 96.3 43.6

0.50 0.37 0.08 0.09

275 303 329 331

76.0 64.8 100 58.2

0.06 0.19 2.57 0.04

TMS

91 227 327 341 342 343

7.72 5.55 20.2 100 57.8 46.9

4.54 3.85 0.67 — 0.56 1.58

96 232 332 345 346 347

8.76 5.73 21.6 100 29.6 71.5

0.73 2.45 0.26 — 3.43 0.19

t-BDMS

313 327 328 329 369

3.52 100 27.5 40.1 3.07

2.95 2.15 2.37 4.45 1.95

318 332 333 334 374

4.15 100 28.3 40.4 3.22

0.42 0.37 0.19 0.06 0.40

a–d




465

Table V-4. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Nitrazepam/nitrazepam-d5 CD Groupc

Ion (m/z)

Nitrazepam Rel. int. Analog’s cont.

Nitrazepam-d5 Ion (m/z) Rel. int. Analog’s cont.

Methyl

220 267 294 295

53.0 100 86.6 60.5

0.00 1.57 0.88 1.30

225 272 298 300

41.3 100 81.4 45.1

4.55 0.00 0.11 0.00

Ethyl

234 281 282 308 309

39.7 65.6 59.9 100 44.5

0.67 0.66 3.75 0.41 0.41

239 286 287 312 314

22.5 66.5 62.8 100 30.1

2.09 0.02 0.00 0.08 0.00

Propyl

295 296 322

54.0 49.1 100

0.47 4.44 0.21

300 301 326

56.6 50.1 100

0.02 0.00 0.10

Butyl

280 309 336 337

74.6 43.7 100 35.4

0.38 0.47 0.20 0.25

284 314 340 341

86.0 45.3 100 24.5

0.10 0.03 0.07 0.09

TMS

306 352 353

34.2 100 61.7

4.13 4.24 4.25

310 356 357

28.6 100 28.2

1.87 0.54 0.24

t-BDMS

292 338 339 380 394

16.6 100 26.3 0.78 6.59

1.23 0.98 1.93 1.58 0.95

297 343 344 385 398

15.7 100 26.4 2.89 5.94

1.44 0.02 0.02 0.09 0.75

a–d


Table V-5. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Temazepam/temazepam-d5 CD Groupc

Ion (m/z)

Temazepam Rel. int. Analog’s cont.

Ion (m/z)

Temazepam-d5 Rel. int. Analog’s cont.

None

228 257 300

100 60.8 89.4

— 2.54 0.37

232 262 305

78.7 67.2 100

— 0.05 0.11

Methyl

255 256 271 314

48.0 33.2 100 29.5

0.97 1.71 0.95 0.59

260 261 276 319

42.5 33.9 100 26.3

1.47 0.11 0.03 0.00

Ethyl

255 256 257 271 273 328

30.0 23.2 24.7 100 33.7 12.9

0.76 0.62 1.37 0.35 4.00 1.08

260 261 262 276 278 333

30.0 24.9 24.4 100 34.0 12.8

3.25 0.78 0.44 0.28 0.19 0.00

Propyl

255 257 271

33.1 31.3 100

4.54 3.04 2.12

260 262 276

32.3 31.2 100

3.20 0.07 0.04

Butyl

255 257 271 300

33.3 37.6 100 12.3

0.40 1.44 0.23 0.70

260 262 276 305

32.2 37.3 100 12.6

3.99 0.07 0.06 0.98



466

Table V-5. (Continued) CD Groupc

Ion (m/z)

Temazepam Rel. int. Analog’s cont.

Temazepam-d5 Ion (m/z) Rel. int. Analog’s cont.

Acetyl

228 256 257 271 300

7.42 22.7 27.3 100 25.7

4.35 1.10 3.76 0.66 0.57

233 261 262 276 305

5.82 24.8 27.4 100 25.2

1.29 0.41 0.05 0.04 0.07

TMS

283 343 345 357 372

28.5 100 38.6 21.3 19.8

0.86 0.58 2.99 0.50 0.84

288 348 350 362 377

28.1 100 39.1 22.2 20.2

0.18 0.31 0.01 0.32 0.33

t-BDMS

255 256 283 357 359 385

28.6 24.3 48.6 100 38.7 10.7

2.14 3.44 0.60 0.42 0.59 0.41

260 261 288 362 364 390

27.7 23.9 46.8 100 39.8 11.0

1.22 0.42 0.17 0.42 0.02 0.55

a–d


Table V-6. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Clonazepam/clonazepam-d4 CD Groupc

Ion (m/z)

Clonazepam Rel. int. Analog’s cont.

Ion (m/z)

Clonazepam-d4 Rel. int. Analog’s cont.

Methyl

248 294 302 329

97.1 100 95.9 91.3

1.20 0.75 1.05 0.74

252 298 306 333

83.5 100 76.5 83.1

1.23 1.37 0.77 0.70

Ethyl

234 262 280 308 316 342

50.1 35.7 62.8 100 60.5 98.4

3.37 3.70 0.76 0.60 2.34 —

238 266 284 312 320 345

45.1 30.0 56.4 100 46.5 62.4

3.30 1.66 2.56 0.93 0.48 —

Propyl

234 315 357

58.3 100 50.6

2.38 2.03 0.63

238 319 361

60.6 100 49.3

4.79 0.67 0.76

Butyl

280 315 336

100 83.3 80.7

0.89 0.61 0.43

284 319 340

100 73.7 71.7

1.59 0.96 1.84

TMS

306 352 372 387

58.3 78.1 39.7 82.0

3.68 3.69 3.85 3.57

310 356 376 391

61.3 87.9 40.8 86.2

1.03 3.23 2.23 2.33

t-BDMS

326 372 373 374 414

12.3 100 26.0 39.3 2.39

1.97 1.35 1.52 1.58 1.25

330 376 377 378 418

12.0 100 26.3 38.8 2.40

4.38 2.37 1.38 0.16 2.72

a–d




467

Table V-7. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — 7-Aminoclonazepam/7-aminoclonazepam-d4 CD Groupc

Ion (m/z)

7-Aminoclonazepam Rel. int. Analog’s cont.

7-Aminoclonazepam-d4 Ion (m/z) Rel. int. Analog’s cont.

[Methyl]3

284 298 299 327 328

14.0 55.6 23.6 100 24.7

1.74 0.93 0.72 0.31 0.96

288 302 303 331 332

14.2 55.3 24.1 100 21.1

4.79 2.56 0.53 0.67 0.23

[Ethyl]2

306 313 341 342

19.5 33.3 100 28.7

0.70 0.82 0.45 1.33

310 317 345 346

22.6 32.8 100 22.9

3.89 0.67 0.73 0.24

[Ethyl]3

354 356 369

100 35.6 64.0

0.16 1.90 0.12

358 360 373

100 34.3 67.4

0.81 0.09 0.56

Propyl

250 256 285 299 327 328

39.7 26.8 28.0 33.8 100 28.9

2.62 4.06 1.40 0.99 0.98 1.79

254 260 289 303 331 322

40.4 24.7 28.3 31.3 100 21.4

3.91 2.15 0.77 0.70 0.73 3.11

[Propyl]2

298 340 341 369 370

27.7 59.4 27.4 100 28.9

2.00 0.92 2.03 0.33 0.79

302 344 345 373 374

26.3 57.7 26.9 100 24.8

1.04 2.59 0.64 0.96 0.32

Butyl

250 256 285 306 341 342

4.30 32.2 40.2 22.1 100 28.7

2.69 3.85 1.11 1.65 0.78 1.51

254 260 289 310 345 346

49.0 33.2 42.8 25.6 100 23.2

3.75 2.47 0.99 1.21 0.84 0.36

[Butyl]2

298 312 354 369 397 398

17.5 17.6 45.8 11.4 100 29.1

1.22 2.81 0.35 1.48 0.22 0.59

302 316 358 373 401 402

18.6 18.0 45.2 11.6 100 27.0

2.04 1.32 0.97 1.05 1.27 0.38

PFP

368 396 402 403 431

23.5 89.4 99.6 69.2 100

0.26 1.73 3.99 1.88 1.52

372 400 406 407 435

23.2 100 97.7 72.2 99.8

0.69 0.75 4.81 0.83 0.71

HFB

418 446 452 453 481

23.2 91.0 97.5 75.9 100

3.06 2.03 — 2.59 2.10

422 450 456 457 485

23.8 98.1 99.4 73.6 100

0.00 0.63 — 1.12 0.72

[TMS]2

314 394 395 414 429 430

30.5 98.3 34.1 37.8 100 44.3

1.30 0.53 2.22 0.34 0.49 1.44

318 398 399 418 433 434

29.1 100 34.7 36.8 98.8 35.6

3.08 1.72 3.12 4.09 4.41 2.57



468


Ion (m/z)

7-Aminoclonazepam Rel. int. Analog’s cont.

Ion (m/z)

7-Aminoclonazepam-d4 Rel. int. Analog’s cont.

t-BDMS

242 328 342 343 344 399

9.65 8.99 100 27.3 39.5 17.7

2.90 4.06 0.59 1.42 1.24 0.56

246 332 346 347 348 403

9.67 9.26 100 27.9 39.5 18.1

2.83 2.04 2.42 1.35 0.41 2.91

[t-BDMS]2

456 457 458

92.2 35.5 42.3

0.51 0.83 1.37

460 461 462

88.4 34.1 40.3

4.85 2.83 0.57

TFA/[TMS]2

410 491 525

20.1 19.8 59.0

3.20 1.77 1.40

414 495 529

26.5 29.2 84.0

2.59 1.25 2.67

TFA/[t-BDMS]2

368 438 552 553 554

15.1 5.21 76.9 30.4 35.5

4.70 3.04 — 1.23 1.53

372 442 556 557 558

12.4 6.48 82.8 34.7 39.0

2.37 4.12 — 3.05 0.54

[TFA]2/t-BDMS

590

2.12

—

594

1.88

—

PFP/TMS

388 468 469 503

25.4 100 29.5 69.0

0.81 0.23 0.81 0.37

392 472 473 507

23.0 100 29.0 64.4

2.75 0.29 1.89 1.34

PFP/[TMS]2

460 540 541 575 576

40.1 100 37.2 96.7 44.9

2.79 0.79 1.39 0.33 1.13

464 544 545 579 580

35.2 100 36.7 91.9 35.3

3.14 0.31 1.53 4.95 2.85

PFP/[t-BDMS]2

440 602 603 604

11.3 100 45.4 50.4

0.96 — 0.32 0.68

444 606 607 608

10.9 100 44.0 48.8

2.51 — 3.56 0.64

HFB/[t-BDMS]2

490 652 653 654

5.87 35.1 14.6 16.4

1.11 — 0.27 0.57

494 656 657 658

6.17 30.7 12.9 14.5

2.55 — 3.05 0.75

a–d


Table V-8. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Prazepam/prazepam-d5 CD Groupc None

a–d

Ion (m/z) 91 241 269 295 296 324

Prazepam Rel. int. Analog’s cont. 78.6 41.1 100 81.2 54.0 38.7

4.09 3.62 2.60 2.22 2.22 1.74

Ion (m/z) 96 246 273 300 301 329

Prazepam-d5 Rel. int. Analog’s cont. 80.7 45.0 100 82.4 61.3 48.5




1.62 1.75 0.63 0.56 0.07 0.08

469

Table V-9. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Lorazepam/lorazepam-d4 CD Groupc

Ion (m/z)

Lorazepam Rel. int. Analog’s cont.

Ion (m/z)

Lorazepam-d4 Rel. int. Analog’s cont.

[Methyl]2

255 305 307 348

9.21 100 65.3 12.1

4.27 — 1.17 0.95

259 309 311 352

8.83 100 65.1 12.3

1.89 — 0.27 11.2

[Ethyl]2

293 319 321 341

24.3 100 67.1 8.17

1.69 — 0.32 0.88

297 323 325 345

23.3 100 65.3 7.68

1.33 — 0.33 1.08

[Propyl]2

293 333 335

31.4 100 66.0

4.00 — 0.87

297 337 339

32.1 100 66.1

3.00 — 0.37

[Butyl]2

347 349

100 68.0

— 1.05

351 353

100 68.2

— 0.15

[HFB]2

407 409

100 36.1

0.25 1.40

411 413

100 33.4

0.75 0.15

[TMS]2

429 430 431

100 34.9 44.6

0.52 0.57 0.86

433 434 435

100 35.3 43.9

4.78 3.06 3.47

[t-BDMS]2

491 493 515

75.4 58.7 32.4

— 0.57 0.55

495 497 519

85.2 65.3 36.7

— 2.34 0.86

a–d


Table V-10a. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Flunitrazepam/flunitrazepam-d3 CD Groupc None

a–d

Ion (m/z) 238 285 286 312 313

Flunitrazepam Rel. int. Analog’s cont. 44.4 91.8 93.6 100 70.7

3.85 2.16 4.23 0.95 0.90

Ion (m/z) 241 288 289 315 316

Flunitrazepam-d3 Rel. int. Analog’s cont. 49.1 97.6 95.0 100 70.0

3.20 1.91 0.17 1.48 0.17


Table V-10b. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Flunitrazepam/flunitrazepam-d7 CD Groupc None

a–d

Ion (m/z) 238 266 285 312

Flunitrazepam Rel. int. Analog’s cont. 43.6 56.0 95.8 100

2.58 0.18 0.43 0.77

Ion (m/z) 245 272 292 318




Flunitrazepam-d7 Rel. int. Analog’s cont. 39.4 44.7 100 99.4

0.59 0.94 0.16 0.00

470

Table V-11a. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — 7-Aminoflunitrazepam/7-aminoflunitrazepam-d3 CD Groupc

7-Aminoflunitrazepam Ion (m/z) Rel. int. Analog’s cont.

7-Aminoflunitrazepam-d3 Ion (m/z) Rel. int. Analog’s cont.

None

283

100

—

286

100

—

[Methyl]2

282 283 311 312

57.5 39.2 100 20.3

0.98 4.29 0.43 1.94

285 286 314 315

55.1 37.8 100 20.5

0.10 0.01 0.21 0.07

Ethyl

283 311 312

41.7 100 20.7

0.42 0.65 3.57

286 314 315

42.5 100 20.7

0.40 0.16 0.00

[Ethyl]2

310 324 339

7.16 100 60.0

2.39 0.27 2.59

313 327 342

5.32 100 54.4

0.04 1.74 0.13

Propyl

268 296 325 326

14.9 100 81.4 19.0

4.48 0.75 1.13 3.68

271 299 328 329

13.1 100 82.7 18.7

0.82 0.46 0.24 0.06

Butyl

268 296 310 339

14.7 100 27.7 95.5

3.16 — 0.87 0.99

271 299 313 342

15.9 100 28.6 97.7

0.31 — 1.47 0.47

Acetyl

297 306 324 325

67.4 24.1 53.1 100

0.64 0.35 0.44 0.34

300 309 327 328

64.5 24.4 53.2 100

0.29 2.03 4.61 0.24

TFA

351

100

—

354

100

—

PFP

401 410 428 429

100 34.5 80.6 91.8

3.48 2.42 2.51 2.94

404 413 431 432

100 35.1 81.8 93.7

0.36 3.52 2.90 0.25

HFB

451

100

—

454

100

—

TMS

327 355

47.3 100

2.92 0.44

330 358

49.3 100

1.31 0.89

TFA/TMS

280 423 424 432 451

22.9 81.9 24.0 17.9 100

1.20 0.53 0.95 0.56 0.50

283 426 427 435 454

26.3 84.1 24.9 18.7 100

2.73 1.22 0.57 2.50 1.17

TFA/t-BDMS

386 436 493

20.7 100 39.7

4.19 4.17 4.12

389 439 496

20.3 100 41.6

1.76 1.35 1.61

PFP/TMS

352 473 474 482 501

15.0 85.2 25.6 21.4 100

1.12 0.25 0.71 0.27 0.26

355 476 477 485 504

15.3 84.7 25.2 21.6 100

2.59 1.34 0.55 1.51 1.06

PFP/t-BDMS

486

100

—

489

100

—

HFB/TMS

280 402 523 524 532 551

17.4 15.4 81.5 25.0 21.2 100

2.41 1.08 0.59 1.30 0.35 0.27

283 405 526 527 535 554

16.6 14.7 79.0 24.2 21.3 100

2.50 1.44 0.98 0.42 1.76 1.31

HFB/t-BDMS

536

100

—

539

100

—

a–d



471

Table V-11b. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — 7-Aminoflunitrazepam/7-aminoflunitrazepam-d7 CD Groupc

Ion (m/z)

7-Aminoflunitrazepam Rel. int. Analog’s cont.

Ion (m/z)

7-Aminoflunitrazepam-d7 Rel. int. Analog’s cont.

None

255 283

62.9 100

0.60 0.24

262 290

68.1 100

0.51 0.00

[Methyl]2

266 282 310 311 312

14.8 57.2 23.5 100 20.5

1.18 2.74 0.33 0.27 0.36

273 289 316 318 319

12.7 57.0 19.8 100 20.6

0.10 0.00 0.03 0.00 0.01

Ethyl

268 282 283 296 310 311

18.5 55.9 43.0 10.8 29.9 100

1.51 1.20 4.79 0.60 0.25 0.68

275 289 290 303 316 318

9.13 56.5 43.5 12.0 26.4 100

0.47 0.12 0.76 0.04 0.09 0.04

[Ethyl]2

266 324 325 339

19.4 100 23.1 60.2

0.99 0.19 0.63 0.19

273 331 332 346

17.6 100 22.2 59.0

0.08 0.00 0.06 0.01

Propyl

268 296 297 325 326

14.1 100 31.5 80.7 17.7

1.29 0.42 1.44 0.32 0.27

275 303 304 332 333

13.3 100 31.8 83.9 17.4

0.93 0.05 1.27 0.00 0.00

Butyl

268 296 297 310 339 340

13.4 100 18.9 28.1 92.5 21.7

2.13 0.30 4.80 0.82 0.04 0.11

275 303 304 317 346 347

14.2 100 20.4 29.6 99.1 22.6

1.46 0.04 0.25 0.00 0.00 0.00

Acetyl

255 296 297 324 325

22.9 27.6 67.4 53.1 100

2.05 3.72 3.32 0.06 0.25

262 303 304 330 332

23.3 30.4 72.6 50.1 100

1.65 0.06 0.56 0.02 0.01

TFA

350 351 378 379

31.2 100 66.5 86.5

1.55 1.41 1.39 1.41

357 358 384 386

30.9 100 55.7 72.3

0.08 0.45 0.02 0.03

PFP

400 401 428 429

37.5 100 75.5 86.0

2.40 2.24 2.30 2.09

407 408 434 436

36.3 100 64.6 70.1

0.47 1.26 1.06 0.80

HFB

450 451 478 479

33.7 100 74.9 85.2

2.75 2.61 2.56 2.69

457 458 484 486

33.3 100 63.8 68.9

0.13 0.28 0.01 0.10

TMS

326 355 356

43.0 100 27.3

1.96 0.66 0.71

333 362 363

44.7 100 27.3

0.07 0.01 0.02

TFA/TMS

423 424 450 451

81.9 24.0 43.5 100

0.47 0.60 0.57 0.60

430 431 456 458

91.5 26.8 39.9 100

0.37 3.75 0.06 0.00



472

Table V-11b. (Continued) CD Groupc

7-Aminoflunitrazepam Ion (m/z)d Rel. int. Analog’s cont.

7-Aminoflunitrazepam-d7 Ion (m/z)d Rel. int. Analog’s cont.

TFA/t-BDMS

436 437 493

100 28.3 37.5

0.19 0.24 0.18

443 444 500

100 28.0 40.6

0.01 0.24 0.00

PFP/TMS

352 473 474 500 501 502

15.0 85.2 25.6 45.4 100 30.3

1.30 0.21 0.29 0.17 0.20 0.26

359 480 481 506 508 509

16.4 92.8 27.8 42.3 100 30.2

0.28 0.53 4.99 0.04 0.00 0.00

PFP/t-BDMS

486

100

—

493

100

—

HFB/TMS

402 523 524 550 551

15.4 81.5 25.0 43.9 100

1.36 0.55 2.11 0.41 0.40

409 530 531 556 558

17.7 89.0 27.9 40.5 100

0.12 0.40 3.60 0.06 0.00

HFB/t-BDMS

296 536 537 593

56.3 100 30.2 29.0

4.73 2.95 3.05 2.81

299 543 544 600

62.9 100 29.8 27.3

1.95 0.22 0.43 0.00

a–d


Table V-12. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — N-Desalkylflurazepam/N-desalkylflurazepam-d4 CD Groupc

N-Desalkylflurazepam Ion (m/z)d Rel. int. Analog’s cont.

N-Desalkylflurazepam-d4 Ion (m/z)d Rel. int. Analog’s cont.

None

259

100

—

263

100

—

Methyl

274 275 283 301 302

100 44.9 34.3 88.0 82.9

3.43 3.10 1.85 — 2.17

278 279 287 304 306

100 44.1 43.2 75.0 91.0

0.39 0.08 0.63 — 0.09

[Methyl]2

239 275 297 316

12.5 100 28.1 31.8

1.43 — 0.37 1.02

243 279 301 320

9.39 100 37.4 33.7

2.49 — 0.00 0.51

Ethyl

259 288 289 297 315 316

26.1 100 51.2 36.9 99.3 80.2

4.08 0.45 4.36 0.44 — 0.17

263 292 293 301 318 320

25.3 100 38.8 46.5 76.4 80.6

1.11 1.28 0.30 2.13 — 0.41

Propyl

259 288 302 311 330

34.9 100 81.8 38.5 71.1

3.96 0.53 0.18 0.38 0.24

263 292 306 315 334

32.3 100 76.8 49.2 74.8

1.79 0.30 0.68 0.63 0.20

Butyl

287 288 316

100 82.8 45.4

— 1.50 0.69

290 292 320

86.3 100 48.4

— 0.37 1.68



473


N-Desalkylflurazepam Ion (m/z)d Rel. int. Analog’s cont.

Acetyl

260 269 288 302

59.4 39.5 100 26.8

TMS

360

t-BDMS

345 346 347 402

a–d

N-Desalkylflurazepam-d4 Ion (m/z)d Rel. int. Analog’s cont.

0.99 0.27 0.26 0.06

264 273 292 306

56.7 48.4 100 25.6

0.80 3.20 0.46 0.70

90.7

0.65

364

100

2.07

100 27.4 40.7 7.58

1.08 2.91 2.25 1.07

349 350 351 406

100 28.6 41.5 819

0.24 1.30 0.12 2.52


Table V-13. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — N-Desmethylflunitrazepam/Ndesmethylflunitrazepam-d4 CD Groupc

N-Desmethylflunitrazepam Ion (m/z)d Rel. int. Analog’s cont.

N-Desmethylflunitrazepam-d4 Ion (m/z)d Rel. int. Analog’s cont.

238

28.9

3.40

242

26.6

1.07

285 286 326

33.7 100 33.0

3.19 0.67 0.45

289 290 329

35.7 100 25.5

0.46 0.09 0.54

Ethyl

299 300 308 326 327

53.0 54.5 32.3 100 51.8

2.03 2.46 0.55 0.52 0.68

303 304 312 329 331

62.7 63.1 50.7 100 40.6

1.75 0.02 2.14 0.99 0.02

Propyl

298 299 313 322 340 341

74.3 95.7 48.8 34.0 100 57.5

4.47 2.04 2.33 0.56 0.45 0.97

301 303 317 326 343 345

72.5 99.0 56.9 52.4 100 44.4

2.55 0.02 0.17 1.80 1.20 0.02

Butyl

298 327 354

100 37.0 93.7

1.74 3.14 0.09

301 331 357

100 43.2 92.6

1.78 0.29 1.00

Acetyl

213 260 302

17.3 100 26.7

2.86 0.60 0.45

216 262 306

12.0 100 30.8

0.66 1.53 0.10

TMS

324 371

29.7 100

3.45 2.14

327 375

26.4 100

2.92 0.11

t-BDMS

310 356 357 413

12.5 100 26.5 2.76

2.43 1.41 1.65 1.21

314 360 361 417

11.9 100 26.4 2.57

0.77 0.13 0.06 0.25

[Methyl]2

a–d




474

Table V-14. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — 2-Hydroxyethylflurazepam/2hydroxyethylflurazepam-d4 CD Groupc

2-Hydroxyethylflurazepam Ion (m/z)d Rel. int. Analog’s cont.

2-Hydroxyethylflurazepam-d4 Ion (m/z)d Rel. int. Analog’s cont.

None

288 313

100 15.3

2.85 1.97

292 317

100 19.2

0.64 1.35

Butyl

183 260 288

16.9 31.0 100

4.24 3.90 1.11

187 264 292

11.3 30.3 100

1.48 0.90 0.67

TMS

260 288 360

26.6 100 16.0

4.74 2.28 1.09

264 292 364

25.5 100 15.5

1.11 0.55 3.42

t-BDMS

345 389 390 391 431

8.87 100 26.7 38.7 2.63

1.30 0.71 0.93 1.76 1.85

349 393 394 395 435

8.83 100 27.9 39.1 2.58

2.73 2.39 1.33 0.10 2.96

aa–d


Table V-15. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Estazolam/estazolam-d5 CD Groupc None

a–d

Estazolam Ion (m/z)d Rel. int. Analog’s cont. 205 239 259 394

66.5 45.4 100 62.7

4.90 1.19 0.78 0.39

Estazolam-d5 Ion (m/z)d Rel. int. Analog’s cont. 210 244 264 299

66.1 27.4 98.9 100

0.52 0.37 0.77 0.20


Table V-16. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Alprazolam/alprazolam-d5 CD Groupc None

a–d

Alprazolam Ion (m/z)d Rel. int. Analog’s cont. 204 273 279 308

76.6 58.5 100 70.7

4.60 4.52 — 0.50

Alprazolam-d5 Ion (m/z)d Rel. int. Analog’s cont. 209 278 284 313

71.4 30.4 100 74.8




0.16 2.78 — 0.07

475

Table V-17. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — α-Hydroxyalprazolam/α-hydroxyalprazolam-d5 CD Groupc

α-Hydroxyalprazolam Ion (m/z)d Rel. int. Analog’s cont.

α-Hydroxyalprazolam-d5 Ion (m/z)d Rel. int. Analog’s cont.

TMS

364 381 383 396 398

3.59 100 38.1 33.4 12.6

4.84 4.52 4.91 4.41 4.46

369 386 388 401 403

3.90 100 39.3 33.7 12.8

3.92 0.45 0.10 0.49 0.09

t-BDMS

381 382 383 423

100 27.9 39.0 2.89

2.54 2.60 2.80 2.31

386 387 388 428

100 28.2 38.7 2.79

0.40 0.16 0.06 0.51

a–d


Table V-18. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — α-Hydroxytriazolam/α-hydroxytriazolam-d4 CD Groupc

α-Hydroxytriazolam Ion (m/z)d Rel. int. Analog’s cont.

α-Hydroxytriazolam-d4 Ion (m/z)d Rel. int. Analog’s cont.

TMS

415

100

—

419

100

—

t-BDMS

380 415 417

6.82 100 70.1

2.38 — 2.34

384 419 421

6.46 100 69.7

3.23 — 1.14

a–d


Table V-19. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Mianserin/mianserin-d3 CD Groupc None

a–d

Mianserin Ion (m/z)d Rel. int. Analog’s cont. 204 273 264

76.6 58.5 46.0

4.60 4.52 0.88

Mianserin-d3 Ion (m/z)d Rel. int. Analog’s cont. 209 278 267




71.4 30.4 46.5

0.16 2.78 0.31

476

Table V-20. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Methaqualone/methaqualone-d7 CD Groupc None a–d

Methaqualone Ion (m/z)d Rel. int. Analog’s cont. 235

100

—

Methaqualone-d7 Ion (m/z)d Rel. int. Analog’s cont. 242

100

—


Table V-21. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Haloperidol/haloperidol-d4 CD Groupc TMS a–d

Haloperidol Ion (m/z)d Rel. int. Analog’s cont. 123

5.05

—

Haloperidol-d4 Ion (m/z)d Rel. int. Analog’s cont. 127

4.44




—

477

Summary of Drug, Isotopic Analogs, and Chemical Derivatization Groups Included in Table VI (Antidepressants) Compound

Isotopic analog


Table #

Imipramine

d3

None

VI-1

Desipramine

d3

None, acetyl, TCA, TFA, PFP, 4-CB, TMS, t-BDMS

VI-2

Trimipramine

d3

None

VI-3

Clomipramine

d3

None

VI-4

Nortriptyline

d3


VI-5

Protriptyline

d3


VI-6

Doxepin

d3

None

VI-7

Dothiepin

d3

None

VI-8

Amitriptyline

d3

None

Maprotiline

d3


VI-9

Table VI — Antidepressants


VI-10

479

Appendix Two — Table VI Cross-Contributions Between Ions Designating the Drugs and Their Isotopically Labeled Analogs in Various Derivatization Forms — Antidepressants Table VI-1. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Imipramine/imipramine-d3 ............................................................................................................. 480 Table VI-2. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Desipramine/desipramine-d3 .......................................................................................................... 480 Table VI-3. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Trimipramine/trimipramine-d3 ....................................................................................................... 480 Table VI-4. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Clomipramine/clomipramine-d3 ..................................................................................................... 481 Table VI-5. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Nortriptyline/nortriptyline-d3 ......................................................................................................... 481 Table VI-6. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Protriptyline/protriptyline-d3 .......................................................................................................... 481 Table VI-7. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Doxepin/doxepin-d3 ....................................................................................................................... 482 Table VI-8. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Dothiepin/dothiepin-d3 ................................................................................................................... 482 Table VI-9. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Amitriptyline/amitriptyline-d3 ........................................................................................................ 483 Table VI-10. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Maprotiline/maprotiline-d3 ............................................................................................................. 483



480 Table VI-1. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Imipramine/imipramine-d3 CD Groupc None

a–d

Imipramie Ion (m/z)d Rel. int. Analog’s cont. 58 85 265 280

89.7 47.4 32.0 20.6

1.75 1.55 3.43 0.79

Imipramine-d3 Ion (m/z)d Rel. int. Analog’s cont. 61 88 268 283

73.3 37.7 0.40 21.9

0.85 1.40 0.26 0.16


Table VI-2. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Desipramine/desipramine-d3 CD Groupc

Desipramine Ion (m/z)d Rel. int. Analog’s cont.

Desipramine-d3 Ion (m/z)d Rel. int. Analog’s cont.

None

44 266

46.4 31.7

— 1.32

47 269

30.0 29.4

— 0.12

Acetyl

114 308

26.3 36.4

1.61 0.99

117 311

26.1 34.2

4.81 0.22

TCA

303 410

1.42 13.0

0.93 —

306 413

1.43 12.3

1.69 —

TFA

362

31.8

1.49

365

25.6

0.21

PFP

412 413

29.3 7.06

0.11 4.00

415 416

32.7 8.03

0.24 0.08

4-CB

276 294 322 501 516 517

1.01 1.42 7.67 0.47 20.6 5.96

1.79 1.25 0.67 4.70 0.56 3.99

279 297 325 504 519 520

0.87 1.20 6.05 0.37 16.3 4.77

1.06 0.50 0.40 2.76 0.63 0.22

TMS

116 143 338

44.8 43.6 13.5

— 3.36 2.03

119 146 341

41.6 41.0 10.7

— 0.59 1.44

t-BDMS

102 380

100 7.84

1.31 1.06

105 383

100 6.94

0.46 1.93

a–d


Table VI-3. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Trimipramine/trimipramine-d3 CD Groupc None

a–d

Trimipramine Ion (m/z)d Rel. int. Analog’s cont. 58 84 294

100 16.9 16.3

1.86 3.16 1.61

Trimipramine-d3 Ion (m/z)d Rel. int. Analog’s cont. 61 87 297

17.5 17.1 21.9




0.01 2.08 0.18

481

Table VI-4. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Clomipramine/clomipramine-d3 CD Groupc None a–d

Clomipramine Ion (m/z)d Rel. int. Analog’s cont. 58 85

100 47.0

Clomipramine-d3 Ion (m/z)d Rel. int. Analog’s cont.

2.53 2.86

61 88

100 48.9

0.12 1.37


Table VI-5. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Nortriptyline/nortriptyline-d3 CD Groupc

Nortriptyline Ion (m/z)d Rel. int. Analog’s cont.

Nortriptyline-d3 Ion (m/z)d Rel. int. Analog’s cont.

None

44

100

2.26

47

100

0.02

Acetyl

44 305 306

30.6 7.33 1.89

1.11 0.45 1.99

47 308 309

42.3 6.92 1.74

0.00 0.71 0.55

TCA

301 372 407

0.80 0.24 1.23

4.92 1.40 —

304 375 410

0.75 0.23 1.10

2.00 4.67 —

TFA

320 359

0.09 2.47

1.52 0.50

323 362

0.08 2.18

4.44 0.19

PFP

409

1.63

0.70

412

1.49

0.25

HFB

240 459

10.4 1.02

0.32 0.80

243 462

10.6 1.22

0.60 0.34

4-CB

294 468 513

3.45 0.61 0.50

— 0.61 1.00

297 471 516

3.25 0.43 0.34

— 0.59 0.79

TMS

116 117 320 334

100 12.1 2.68 0.16

0.45 4.33 0.39 3.02

119 120 323 337

100 11.9 3.17 0.20

0.27 0.11 1.27 2.77

t-BDMS

102 158 159 320 362 376

5.15 100 16.4 4.08 1.81 0.29

2.95 0.04 1.17 1.06 0.13 1.14

105 161 162 323 365 379

5.22 100 16.4 3.46 1.48 0.25

2.94 0.49 0.30 1.21 1.61 1.48

a–d


Table VI-6. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Protriptyline/protriptyline-d3 CD Groupc

Protriptyline Ion (m/z)d Rel. int. Analog’s cont.

Protriptyline-d3 Ion (m/z)d Rel. int. Analog’s cont.

None

44 70

40.6 61.7

1.87 2.30

47 73

57.3 67.4

0.03 0.05

Acetyl

114 305 306

5.81 10.6 2.55

1.79 0.57 0.76

117 308 309

5.91 8.92 2.18

2.03 0.38 0.83

TCA

299 407

0.37 2.25

1.03 —

302 410

0.38 2.10

4.78 —



482

Table VI-6. (Continued) CD Groupc

Protriptyline Ion (m/z)d Rel. int. Analog’s cont.

Protriptyline-d3 Ion (m/z)d Rel. int. Analog’s cont.

TFA

345 359 360

0.06 4.71 1.10

3.64 0.15 0.47

348 362 363

0.06 5.14 1.22

0.00 0.24 0.07

PFP

336 395 409 410

0.05 0.08 5.00 1.23

1.58 3.18 0.14 0.58

369 398 412 413

0.05 0.07 3.81 0.92

0.74 0.00 0.25 0.07

HFB

240 268 445 459 460

2.68 0.71 0.07 5.29 1.39

0.30 0.60 1.97 0.06 0.34

243 271 448 462 463

2.64 0.70 0.07 5.61 1.46

0.21 1.21 0.00 0.35 0.11

4-CB

322 468 513 514

1.17 0.80 4.21 1.24

1.92 0.78 0.74 0.91

325 471 516 517

0.96 9.56 2.88 0.85

0.87 0.56 0.49 0.27

TMS

116 142 320 335

100 51.3 3.95 2.46

2.33 1.98 2.86 2.18

119 145 323 338

100 52.7 4.37 2.87

0.32 0.39 1.36 2.16

t-BDMS

158 184 320 321 377

28.0 41.3 82.2 24.2 2.38

1.15 1.06 1.03 1.52 1.15

161 187 323 324 380

28.1 42.4 81.6 24.4 2.36

0.81 1.75 1.25 0.47 1.79

a–d


Table VI-7. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Doxepin/doxepin-d3 CD Groupc None

a–d

Doxepin Ion (m/z)d Rel. int. 58 84 294

100 16.9 16.3

Analog’s cont. 1.86 3.16 1.61

Doxepin-d3 Ion (m/z)d Rel. int. Analog’s cont. 61 87 297

17.5 17.1 21.9

0.01 2.08 0.18


Table VI-8. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Dothiepin/dothiepin-d3 CD Groupc None a–d

Dothiepin Ion (m/z)d Rel. int. Analog’s cont. 58

100

1.84

Dothiepin-d3 Ion (m/z)d Rel. int. Analog’s cont. 61

100




0.04

483

Table VI-9. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Amitriptyline/amitriptyline-d3 CD Groupc None a–d

Amitriptyline Ion (m/z)d Rel. int. Analog’s cont. 58

100

Amitriptyline-d3 Ion (m/z)d Rel. int. Analog’s cont.

0.38

61

100

0.02


Table VI-10. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Maprotiline/maprotiline-d3 CD Groupc

Maprotiline Ion (m/z)d Rel. int. Analog’s cont.

None

44

100

—

Acetyl

100 291 292 319

10.5 100 23.5 33.3

TCA

304 393

TFA

Maprotiline-d3 Ion (m/z)d Rel. int. Analog’s cont. 47

100

—

2.87 0.52 0.66 0.63

103 294 295 322

11.5 100 23.7 3.10

1.81 0.21 0.11 0.30

4.94 100

1.22 —

307 396

5.18 100

0.57 —

345 346 373

100 23.5 1.25

0.14 0.35 0.21

348 349 376

100 23.7 1.18

0.21 0.06 0.30

PFP

304 395 396 423

0.82 100 24.1 0.95

0.29 0.09 0.32 0.00

307 398 399 426

0.80 100 24.3 0.93

0.74 0.23 0.07 0.31

HFB

240 254 304 445 446 473

4.52 3.61 0.46 100 25.6 0.77

0.74 0.48 0.37 0.06 0.28 0.00

243 257 307 448 449 476

4.72 3.56 0.48 100 26.4 0.77

1.10 0.23 1.97 0.26 0.07 0.32

4-CB

482 499 500

1.90 100 29.2

1.01 0.75 1.00

485 502 503

1.89 100 29.3

1.45 0.47 0.25

TMS

116 277 334 349

100 3.26 2.20 10.2

0.65 1.76 2.32 0.28

119 280 337 352

100 3.08 2.38 10.8

0.25 0.48 1.33 1.36

t-BDMS

102 158 306 334 335 391

50.8 43.1 17.7 100 30.4 8.13

0.87 0.71 0.32 0.07 3.42 0.28

105 161 309 337 338 394

48.2 41.9 17.7 100 31.0 8.58

0.27 0.46 0.98 1.24 0.42 1.61

a–d




485

Summary of Drugs, Isotopic Analogs, and Chemical Derivatization Groups Included in Table VII (Others) Compound

Isotopic analog


Table #

d3

None

VII-1

Cotinine

d3

None

VII-2

Nicotine

d4

None

VII-3

5-α-Estran-3α-ol-17-one

d3

None, acetyl, TMS

VII-4

5-β-Estran-3α-ol-17-one

d3

None, acetyl, TMS

VII-5

Stanozolol

d3

None, acetyl, [TMS]2, t-BDMS

VII-6

3-Hydroxystanozolol

d3

[TMS]2, [t-BDMS]2

VII-7

Promethazine

d3

None

VII-8

Chlorpromazine

d3

None

VII-9

Acetaminophen

d4

None, [acetyl]2, TCA, TFA, PFP, HFB, 4-CB, TMS, [TMS]2, t-BDMS, [t-BDMS]2

VII-10

Clonidine

d4

None, acetyl, [acetyl]2, TMS, [TMS]2, [t-BDMS]2

VII-11

Chloramphenicol

d5

None, [acetyl]2, TMS, [TMS]2

VII-12

Melatonin

d7

None, acetyl, TFA, PFP, HFB, TMS

VII-13

Diphenhydramine

Table VII — Others


487

Appendix Two — Table VII Cross-Contributions Between Ions Designating the Drugs and Their Isotopically Labeled Analogs in Various Derivatization Forms — Others Table VII-1. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Diphenhydramine/diphenhydramine-d3 ........................................................................................... 488 Table VII-2. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Cotinine/cotinine-d3 ......................................................................................................................... 488 Table VII-3. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Nicotine/nicotine-d4 ......................................................................................................................... 488 Table VII-4. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — 5-α−Estran−3α−ol-17-one/5-α−estran−3α−ol-17-one-d3 ............................................................... 488 Table VII-5. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — 5-β−Estran−3α−ol-17-one/5-β−estran−3α−ol-17-one-d3 ............................................................... 489 Table VII-6. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Stanozolol/stanozolol-d3 .................................................................................................................. 489 Table VII-7. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — 3-Hydroxystanozolol/3-hydroxystanozolol-d3 ................................................................................. 489 Table VII-8. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Promethazine/promethazine-d3 ........................................................................................................ 490 Table VII-9. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Chlorpromazine/chlorpromazine-d3 ................................................................................................. 490 Table VII-10. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Acetaminophen/acetaminophen-d4 ................................................................................................... 490 Table VII-11. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Clonidine/clonidine-d4 ..................................................................................................................... 491 Table VII-12. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Chloramphenicol/chloramphenicol-d5 ............................................................................................. 492 Table VII-13. Relative intensity and cross-contribution data of ions with potential for designating the analyte and the adapted internal standard — Melatonin/melatonin-d7 .................................................................................................................... 492



488 Table VII-1. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Diphenhydramine/diphenhydramine-d3 CD Groupc None a–d

Diphenhydramine Ion (m/z)d Rel. int. Analog’s cont. 58

100

0.93

Diphenhydramine-d3 Ion (m/z)d Rel. int. Analog’s cont. 61

100

0.09


Table VII-2. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Cotinine/cotinine-d3 CD Groupc None

a–d

Cotinine Ion (m/z)d Rel. int. 98 175 176

100 10.0 37.0

Analog’s cont. 1.82 2.04 1.89

Cotinine-d3 Ion (m/z)d Rel. int. 101 178 179

100 11.0 41.0

Analog’s cont. 0.25 3.00 0.25


Table VII-3. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Nicotine/nicotine-d4 CD Groupc None

a–d

Nicotine Ion (m/z)d Rel. int. 92 133 161

7.00 36.0 21.0

Analog’s cont. 17.0 — 2.12

Nicotine-d4 Ion (m/z)d Rel. int. 96 136 165

6.00 22.0 19.0

Analog’s cont. 0.13 — 0.02


Table VII-4. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — 5-α−Estran−3α−ol-17-one/5-α−estran−3α−ol17-one-d3 CD Groupc

5-α-Estran-3α-ol-17-one Ion (m/z)d Rel. int. Analog’s cont.

5-α-Estran-3α-ol-17-one-d3 Ion (m/z)d Rel. int. Analog’s cont.

None

276

100

2.47

279

100

0.21

Acetyl

258 318

100 7.60

1.05 1.19

261 321

100 18.3

0.53 0.53

TMS

129 333 348

34.7 100 25.6

— 0.45 0.83

130 336 351

43.3 87.4 11.4

— 1.91 4.03

a–d




489

Table VII-5. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — 5-β−Estran−3α−ol-17-one/5-β−estran−3α−ol-17one-d3 CD Groupc

5-β-Estran-3α-ol-17-one Ion (m/z)d Rel. int. Analog’s cont.

5-β-Estran-3α-ol-17-one-d3 Ion (m/z)d Rel. int. Analog’s cont.

None

276

100

—

279

95.9

—

Acetyl

258 318

100 33.9

1.77 1.18

261 321

67.5 24.9

0.56 0.24

TMS

216 258 333 348

86.8 100 47.3 8.08

— 3.73 1.06 2.05

217 261 336 351

100 76.4 34.5 6.12

— 0.43 2.10 1.99

a–d


Table VII-6. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Stanozolol/stanozolol-d3 CD Groupc

Stanozolol Ion (m/z)d Rel. int.

None

328

61.5

Acetyl

327

[TMS]2

143 473

t-BDMS

358 386 387 442

a–d

Analog’s cont.

Stanozolol-d3 Ion (m/z)d Rel. int. Analog’s cont.

—

331

59.2

—

21.2

—

330

20.7

—

100 7.60

3.49 4.98

146 476

100 7.62

2.02 3.55

12.0 100 30.4 7.47

3.49 1.97 4.34 1.97

361 389 390 445

11.7 100 31.6 7.19

1.44 1.33 0.56 2.28


Table VII-7. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — 3-Hydroxystanozolol/3-hydroxystanozolol-d3 CD Groupc

3-Hydroxystanozolol Ion (m/z)d Rel. int. Analog’s cont.

3-Hydroxystanozolol-d3 Ion (m/z)d Rel. int. Analog’s cont.

[TMS]2

473 488 489

96.2 36.8 15.1

— 3.52 4.63

476 491 492

100 39.4 15.7

— 3.94 1.58

[t-BDMS]2

459 515 516 517

26.0 100 71.4 28.5

2.55 — 1.31 3.10

462 518 519 520

24.6 100 71.5 28.4

4.23 — 2.63 0.77

a–d




490 Table VII-8. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Promethazine/promethazine-d3 CD Groupc None a–d

Promethazine Ion (m/z)d Rel. int. Analog’s cont. 72 284

100 6.91

1.18 1.51

Promethazine-d3 Ion (m/z)d Rel. int. Analog’s cont. 75 287

100 6.49

0.58 1.21


Table VII-9. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Chlorpromazine/chlorpromazine-d3 CD Groupc None a–d

Chlorpromazine Ion (m/z)d Rel. int. Analog’s cont. 58

100

2.26

Chlorpromazine-d3 Ion (m/z)d Rel. int. Analog’s cont. 61

100

0.36


Table VII-10. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Acetaminophen/acetaminophen-d4 CD Groupc

Acetaminophen Ion (m/z)d Rel. int. Analog’s cont.

Acetaminophen-d4 Ion (m/z)d Rel. int. Analog’s cont.

None

109

100

—

112

100

—

[Acetyl]2

109 151 193 235

100 53.5 36.4 3.09

0.40 0.15 0.09 0.23

113 155 197 239

100 56.0 38.2 3.33

0.02 0.01 0.02 0.05

TCA

108 134 255 297

100 18.0 36.5 15.6

0.32 0.83 0.40 0.46

112 138 259 301

100 19.1 39.2 17.2

1.48 0.89 3.49 3.59

TFA

108 205 206 247

100 63.9 6.14 33.7

0.76 0.56 1.10 0.54

112 209 210 251

100 63.7 6.23 34.9

0.04 0.07 0.10 0.04

PFP

108 208 236 255 297

100 3.72 2.86 65.7 36.4

0.46 0.65 0.64 0.27 0.29

112 212 240 259 301

100 3.60 2.96 62.9 35.6

0.20 0.37 4.24 0.14 0.11

HFB

80 108 134 286 305 347

9.25 100 5.89 3.27 50.4 27.9

4.39 0.40 4.63 0.26 0.21 0.20

84 112 138 290 309 351

8.96 100 5.96 3.18 49.0 27.6

0.56 0.14 0.46 0.35 0.07 0.07

4-CB

108 243 359 401

100 3.43 34.1 19.1

0.94 1.04 1.02 0.75

112 247 363 405

100 3.28 33.9 19.3

0.04 0.04 0.01 0.01



491

Table VII-10. (Continued) CD Groupc

Acetaminophen Ion (m/z)d Rel. int. Analog’s cont.

Acetaminophen-d4 Ion (m/z)d Rel. int. Analog’s cont.

TMS

166 181 208 223

84.3 100 23.9 75.9

1.39 0.47 0.40 0.39

170 185 212 227

78.7 100 23.7 73.9

0.33 0.34 0.26 0.20

[TMS]2

181 206 223 280 295

26.2 100 17.7 87.3 64.5

2.86 0.39 1.55 0.23 0.25

185 210 227 284 299

27.1 100 18.9 89.0 65.3

0.18 0.43 0.32 0.40 0.57

t-BDMS

166 208 209 250 265

11.4 100 22.0 2.46 31.0

2.49 0.12 0.28 0.55 0.06

170 212 213 254 269

11.6 100 21.6 2.63 31.6

0.38 0.12 0.05 0.03 0.03

[t-BDMS]2

223 248 308 322 323 379

14.0 44.2 17.9 100 35.1 5.93

0.71 0.24 0.37 0.13 0.75 0.14

227 252 312 326 327 383

14.2 43.1 18.2 100 34.9 6.06

0.42 4.32 0.34 0.47 0.30 1.85

a–d


Table VII-11. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Clonidine/clonidine-d4 CD Groupc

Clonidine Ion (m/z)d Rel. int.

Analog’s cont.

Clonidine-d4 Ion (m/z)d Rel. int. Analog’s cont.

None

194 229

32.8 100

2.90 1.45

198 233

32.2 100

0.60 10.9

Acetyl

194 208 236 238

95.9 9.27 100 32.7

2.83 3.33 2.89 2.82

198 212 240 242

99.9 10.6 100 32.3

0.37 1.87 0.48 0.23

[Acetyl]2

194 236 238 278 280

87.4 100 33.7 71.8 24.3

0.79 0.82 0.72 0.28 0.23

198 240 242 282 284

86.7 100 33.2 71.7 23.9

0.25 0.34 0.46 0.56 0.03

TMS

142 266 268

38.8 100 36.9

2.74 1.35 3.46

146 270 272

44.7 100 37.6

4.70 2.92 1.42

[TMS]2

214 322 338 340

36.0 17.3 100 42.5

1.34 0.46 0.89 2.73

218 326 342 344

40.2 14.4 100 42.7

2.83 4.43 3.74 0.44

[t-BDMS]2

252 254

100 39.8

0.44 4.23

256 258

100 39.9

1.81 0.24

a–d




492 Table VII-12. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Chloramphenicol/chloramphenicol-d5 CD Groupc

Chloramphenicol Ion (m/z)d Rel. int. Analog’s cont.

Chloramphenicol-d5 Ion (m/z)d Rel. int. Analog’s cont.

None

115 162

26.2 23.9

— 3.25

120 167

17.9 22.4

— 0.11

[Acetyl]2

153

100

—

158

90.2

—

TMS

224 225 235 252 321 351

99.6 17.2 11.9 14.1 14.3 8.39

0.79 3.37 1.49 1.85 0.67 0.43

229 230 240 257 326 356

100 17.1 12.4 15.7 15.6 9.79

0.19 1.28 0.88 0.36 0.71 1.13

[TMS]2

297 298

79.8 20.3

0.21 1.62

302 303

84.1 21.0

0.12 0.42

a–d


Table VII-13. Relative intensity and cross-contribution dataa of ionsb with potential for designating the analyte and the adapted internal standard — Melatonin/melatonin-d7 CD Groupc

Melatonin Ion (m/z)d Rel. int.

Analog’s cont.

Melatonin-d7 Ion (m/z)d Rel. int. Analog’s cont.

None

160 173 174 232

100 97.9 13.1 20.8

4.17 3.19 4.54 2.25

162 176 177 239

100 79.3 26.5 18.5

0.84 0.41 0.34 0.25

Acetyl

117 145 160 173 174 274

14.4 18.7 98.3 100 14.5 15.6

4.53 3.42 0.81 0.26 1.24 0.88

119 147 162 176 177 281

14.5 17.6 100 92.4 16.6 15.1

0.84 3.11 0.62 0.12 0.13 2.90

TFA

144 159 256 269 270 328

11.3 19.9 14.8 100 15.0 9.55

1.93 1.60 2.03 0.63 2.15 1.00

146 161 258 272 273 335

13.6 21.5 17.1 100 22.8 9.49

0.29 1.49 1.37 0.07 0.02 0.00

PFP

159 306 319 320

24.1 15.4 100 15.9

2.95 2.26 0.52 1.58

161 308 322 323

23.6 17.0 100 23.5

3.60 2.39 0.54 0.43

HFB

159 356 359 428

25.8 13.5 100 8.17

2.64 1.41 0.43 0.76

161 358 372 435

27.0 14.4 100 5.81

1.97 1.64 0.15 0.68

TMS

232 245 246 304

100 74.1 16.6 18.5

— 0.68 2.31 0.70

234 248 249 311

100 73.8 19.0 12.6

— 0.94 0.42 0.20

a–d




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