Mass spectrometry in drug metabolism and disposition : basic principles and applications

This book examines the background, industrial context, process, analytical methodology, and technology of metabolite identification. It emphasizes the applications of metabolite identification in drug research. While primarily a textbook, the book also functions as a comprehensive reference to those in the industry. The authors have worked closely together and combine complementary backgrounds to bring technical and cultural awareness to this very important endeavor while serving to address needs within academia and industry It also contains a variety of problem sets following specific sections in the text.

Author Notes

MIKE S. LEE, PhD, is President of Milestone Development Services. His recent work has involved the development of automated orthogonal control systems for electrospray ionization. Formerly, Dr. Lee was director of analytical research and development at Bristol-Myers Squibb (BMS) Pharmaceutical Research Institute where he led interdisciplinary teams that contributed to the Food and Drug Administration's approval of Buspar® and Serzone®, and the accelerated development and approval of Taxol®. In addition, he has authored over forty scientific papers and issued patents.

MINGSHE ZHU, PhD , is a drug metabolism researcher at Bristol-Myers Squibb, where he leads a team that investigates biotransformation in new drug discovery and preclinical drug metabolism and pharmacokinetics in development. His teams have provided key metabolism and disposition information for regulatory approval of Abilify® and NDA submission of Dapagliflozin. Dr. Zhu's research interests include LC/MS technology, optimization of ADME properties, metabolic activation, and regulatory drug metabolism. He has been frequently invited to speak and teach short courses at conferences/workshops and has coauthored over sixty research articles and one book.

ForewordTom Baillie

PrefaceMike Lee and Mingshe Zhu

Contributors

Part I Basic Concepts of Drug Metabolism and Disposition

1 Progression of Drug MetabolismRonald E. White

2 Common Biotransformation ReactionsBo Wen and Sidney D. Nelson

3 Metabolic Activation of Organic Functional Groups Utilized in Medicinal ChemistryAmit S. Kalgutkar

4 Drug-Metabolizing Enzymes, Transporters, and Drug-Drug InteractionsSteven W. Louie and Magang Shou

5 Experimental Models of Drug Metabolism and DispositionGang Luo and Chuang Lu and Xinxin Ding and Donglu Zhang

6 Principles of Pharmacokinetics: Predicting Human Pharmacokinetics in Drug DiscoveryTakehito Yamamoto and Akihiro Hisaka and Hiroshi Suzuki

7 Drug Metabolism Research as Integral Part of Drug Discovery and Development ProcessesW. Griffith Humphereys

Part II Mass Spectrometry in Drug Metabolism: Principles and Common Practice

8 Theory and Instrumentation of Mass SpectrometryGérard Hopfgartner

9 Common Liquid Chromatography-Mass Spectrometry (LC-MS) Methodology for Metabolite IdentificationLin Xu and Lewis J. Klunk and Chandra Prakash

10 Mass Spectral InterpretationLi-Kang Zhang and Birendra N. Pramanik

11 Techniques to Facilitate the Performance of Mass Spectrometry: Sample Preparation, Liquid Chromatography, and Non-Mass-Spectrometric DetectionMark Hayward and Maria D. Bacolod and Qing Ping Han and Manuel Cajina and Zack Zou

Part III Applications of New LC-MS Techniques in Drug Metabolism and Disposition

12 Quantitative In Vitro ADME Assays Using LC-MS as a Part of Early Drug Metabolism ScreeningWalter Korfmacher

13 High-Resolution Mass Spectrometry and Drug Metabolite IdentificationRussell J. Mortishire-Smith and Haiying Zhang and Kevin P. Bateman

14 Distribution Studies of Drugs and Metabolites in Tissue by Mass Spectrometric ImagingRichard F. Reich and Daniel P. Magparangalan and Timothy J. Garrett and Richard A. Yost

15 Use of Triple Quadrupole-Linear Ion Trap Mass Spectrometry as a Single LC-MS Platform in Drug Metabolism and PharmacokineticsWenying Jian and Ming Yao and Bo Wen and Elliott B. Jones and Mingshe Zhu

16 Quantitative Drug Metabolism with Accelerator Mass SpectrometryJohn S. Vogel and Peter Lohstroh and Brad Keck and Stephen R. Dueker

17 Standard-Free Estimation of Metabolite Levels Using Nanospray Mass Spectrometry: Current Statutes and Future DirectionsJing-Tao Wu

18 Profiling and Characterization of Herbal Medicine and Its Metabolites Using LC-MSZeper Abliz and Ruiping Zhang and Ping Geng and Dongmei Dai and Jiuming He and Jian Liu

19 Liquid Chromatography Mass Spectrometry Bioanalysis of Protein Therapeutics and Biomarkers in Biological MatricesFumin Li and Qin C. Ji

20 Mass Spectrometry in the Analysis of DNA, Protein, Peptide, and Lipid Biomarkers of Oxidative StressStacy L. Gelhaus and Ian A. Blair

21 LC-MS in Endogenous Metabolite Profiling and Small-Molecule Biomarker DiscoveryMichael D. Reily and Petia Shipkova and Serhiy Hnatyshyn

Appendix

Index.

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Bound With These Titles

On Order

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Author Notes

Table of Contents