Identification and Quantification of Drugs, Metabolites, Drug Metabolizing Enzymes, and Transporters. Concepts, Methods and Translational Sciences. Edition No. 2

Table of Contents

Part I: Techniques for Identifying and Quantifying Drugs and Metabolites 1. Bioanalysis of Small and Large Molecule Drugs, Metabolites, and Biomarkers by LC-MS 2. Recent advances in mass spectrometric and other analytical techniques for the identification of drug metabolites 3. High-resolution mass spectrometry-based data acquisition and data mining technologies for detecting and characterizing drug metabolites and herbal medicine components 4. Metabolite Generation and Metabolite Characterization by NMR 5. Application of SFC for bioanalysis 6. AMS in drug development: Exploring the current utility of AMS and future opportunities for Absolute Bioavailability and ADME investigations

Part II: Drug Metabolism Enzymes, Transporters and Drug-Drug Interaction 7. Using in vitro methods to determine P450s responsible for metabolism and discrimination from other oxidative pathways 8. Evaluation of the clearance mechanism of non-CYP enzymes mediated drug metabolism and DDI as a victim drug 9. In vitro Characterization and In Vitro to In Vivo Predictions of Drug-Drug Interactions 10. Role of Transporters in drug disposition and Drug-drug Interactions 11. Mechanisms and Clinical Relevance of Pharmacokinetic-based Clinical Drug-drug Interactions for Drugs Recently Approved by the U.S. Food and Drug Administration 12. Quantifying drug metabolism enzymes and transporters by LC-MS/MS proteomics 13. Protein Drug-Drug Interactions for Disease Modifying Modalities

Part III: Strategy Related to Drug Metabolism and Safety 14. Metabolites in safety testing (MIST) 15. The Use of Stable Isotopes in Drug Metabolism Studies 16. Assessment of Stereoselectivity in Pharmacology, Toxicology and Drug Metabolism 17. Progress of De-Risking Strategies for Drug-Induced Liver Injury (DILI) In the Last Two Decades 18. Predictive and Translational Models for Renal Drug Safety Evaluation 19. Immunogenicity: An Introduction to Its Role in the Safety and Efficacy of Biotherapeutics

Part IV: Translational Sciences 20. Application of Genetically-Modified Rodent Models in Drug Discovery and Development for Translation of Clinical ADME Properties 21. Advances in CRISPR Technologies Enable Novel in vitro Tools for ADME Studies 22. In vitro-In vivo Extrapolation of Human Hepatic and Renal Clearance 23 The Role of Mathematical Modeling in Translational Science 24. PK/PD Driven Starting and Effective Human Dose Determination for Immuno-Oncology Drugs

Authors

Shuguang Ma Principal Scientist, Department of Drug Metabolism and Pharmacokinetics, Genentech Inc.. Dr. Ma is currently a Principal Scientist in the Department of Drug Metabolism and Pharmacokinetics at Genentech Inc. Previously he was a Senior Principal Scientist at Schering-Plough (now Merck) and a Senior Scientist at Amgen. He received his Ph.D. in Analytical Chemistry from Purdue University under the direction of Professor R. Graham Cooks. He also had two years of postdoctoral training in biological mass spectrometry at Vanderbilt University School of Medicine under Professor Richard Caprioli. Dr. Ma has authored 55 research articles in peer-reviewed journals and 4 book chapters, covering broad areas of mass spectrometry and its applications. His current research interests include the development of novel LC/MS-based techniques for metabolite detection and investigation of biotransformation and bioactivation of xenobiotics. Swapan Chowdhury Director of DMPK, Takeda Pharmaceutical International Co., Cambridge, MA, USA. Dr. Chowdhury is currently a Director of DMPK at Takeda Pharmaceutical International Co. in Cambridge, MA, responsible for evaluating metabolism, toxicity, and potential for drug-drug interaction due to modulation of activities of metabolizing enzymes and transporters by compounds in discovery and development. Dr. Chowdhury obtained his Ph.D. from the University of Alberta in 1987. After spending a year and a half as a post-doctoral fellow at the University of Toronto, Dr. Chowdhury joined Rockefeller University as a Research Associate in the laboratory of Professor Brian Chait. At Rockefeller University, Dr. Chowdhury was involved in the early stage of the development of atmospheric pressure ionization (API) mass spectrometry. This early research on API led to the introduction of a novel API system for LC/MS. After leaving Rockefeller University, he worked on the applications of liquid chromatography/mass spectrometry techniques at several non-academic organizations, including at Schering-Plough Research Institute (SPRI), where he worked for fifteen years in the Department of Drug Metabolism and Pharmacokinetics. The focus of his research at SPRI was to investigate the biotransformation of drugs in support of drug discovery and development. He was involved with the development and registration of a number of pharmaceuticals including Temodar, Clarinex, Zetia, Noxafil, Nasonex/Asmanex, and Victrelis. Dr. Chowdhury is an author of nearly 100 original publications covering a broad area of drug metabolism and drug-drug interaction and analytical technologies to evaluate them.