The pioneering guide to solving real-world problems in drug metabolism using mass spectrometry Mass spectrometry has become the predominant analytical tool for drug metabolism and pharmacokinetics research in modern drug discovery and development. This book represents a coherent integration of all relevant background knowledge and detail surrounding the analytical technologies in this new multidisciplinary field. With chapters written by internationally renowned authors, the book provides details on: * Basic concepts of drug metabolism and pharmacokinetics * The principles and common practice of mass spectrometry in drug metabolism * Applications of new LC/MS techniques in drug metabolism and disposition Mass Spectrometry in Drug Metabolism and Disposition examines fundamental aspects and practical considerations of using mass spectrometry in drug metabolism such as biotransformation reactions, metabolizing enzymes, transporters and drug-drug interactions, drug metabolism in drug design and development, theory and instrumentation of mass spectrometry, and LC/MS approaches to drug metabolism and mass spectral interpretation. Exciting details on new mass spectrometry technology and novel applications used in the frontiers of pharmaceutical research, including high-resolution mass spectrometry in metabolite identification, imaging mass spectrometry in drugtissue distribution, accelerator mass spectrometry in microdosing, as well as theanalyses of metabolomes, herbal medicine, biomarkers, and biologics by various mass spectrometers are also highlighted in the book. This unique book serves as both a textbook for students as well as a comprehensive reference for pharmaceutical professionals, offering fresh and exciting solutions in the ongoing effort to design and develop drugs that are both effective and safe.

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(r) and Serzone(r), and the accelerated development and approval of Taxol(r). 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(r) 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.

Leseprobe

Editors'' Preface. Foreword. Part I. Basic Concepts of Drug Metabolism and Disposition. 1. The Progression of Drug Metabolism. 2. Common Biotransformation Reactions. 3. Metabolic Activation of Organic Functional Groups Utilized in Medicinal Chemistry. 4. Drug Metabolizing Enzymes, Transporters and Drug-Drug Interactions. 5. Experimental Models of Drug Metabolism and Disposition. 6. Principles of Pharmacokinetics: Predicting Human Pharmacokinetics. 7. Drug Metabolism Research as an Integral Part of the Drug Discovery and Development Processes. Part II. Mass Spectrometry in Drug Metabolism: Principles and Common Practice. 8. Theory and Instrumentation of Mass Spectrometry. 9. Common Liquid Chromatography-Mass Spectrometry (LC-MS) Methodology for Metabolite Identification. 10. Mass Spectral Interpretation. 11. Techniques to Facilitate the Performance of Mass Spectrometry: Sample Preparation, Liquid Chromatography and Non-Mass Spectrometric Detection. 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 Screening. 13. High Resolution Mass Spectrometry and Drug Metabolite Identification. 14. Distribution Studies of Drugs and Metabolites in Tissue by Mass Spectrometric Imaging. 15. Use of Triple Quadrupole-Linear Ion Trap Mass Spectrometry as a Single LC/MS Platform in Drug Metabolism and Pharmacokinetics Studies. 16. Quantitative Drug Metabolism with Accelerator Mass Spectrometry. 17. Standard-Free Estimation of Metabolite Levels Using Nanospray Mass Spectrometry: Current Statutes and Future Directions. 18. Profiling and Characterization of Herbal Medicine and their Metabolites using LC/MS. 19. Liquid Chromatography Mass Spectrometry Bioanalysis of Proteins in Biological Matrices. 20. Mass Spectrometry in the Analysis of DNA, Protein, Peptide, and Lipid Biomarkers of Oxidative Stress. 21. LC-MS in Endogenous Metabolite Profiling and Small Molecule Biomarker Discovery. Appendices. Mass shifts and mass defect shifts of common metabolites from the parent drugs. Index.