Biotransformation and Metabolite Elucidation of Xenobiotics: Nassar/Elucidation of Xenobiotics

The goal of this book is to improve the readers' knowledge of metabolite elucidation in drug metabolism by exposing them to in depth coverage of the biotransformation of xenobiotics, strategies for identifying and characterizing metabolites, FDA guidelines, and case studies on how to improve the decision-making process in structural modification of drug candidates to reduce toxicity. The book consists of 8 chapters; it first provides an introduction on biotransformation of xenobiotics, and then presents modern approaches and strategies for dealing with metabolite characterization, using tools such as LC-MS, H-D exchange, stable isotopes LC-MS-NMR, and radiolabeled compounds. Also, strategies for dealing with reactive intermediates in drug discovery and development are presented as well as case studies on improving the decision-making process in the structural modification of drug candidates. The last chapter discusses the regulatory perspectives of safety testing of drug metabolites and why, how, and when to test their safety.Content: Chapter 1 Human Biotransformation (pages 1–77): Andrew Parkinson, Brian W. Ogilvie, Brandy L. Paris, Tiffini N. Hensley and Greg J. Loewen Chapter 2 Analytical Tools and Approaches for Metabolite Identification in Drug Metabolism (pages 79–123): Yongmei Li Chapter 3 Tools of Choice for Accelerating Metabolite Identification: Mass Spectrometry Technology Drives Metabolite Identification Studies Forward (pages 125–162): Ala F. Nassar Chapter 4 Improving Drug Design: Considerations for the Structural Modification Process (pages 163–216): Ala F. Nassar Chapter 5 Case Study: The Unanticipated Loss of N2 from Novel DNA Alkylating Agent Laromustine by Collision?Induced Dissociation: Novel Rearrangements (pages 217–228): Ala F. Nassar, Jing Du, David Roberts, Kevin Lin, Mike Belcourt, Ivan King and Tukiet T. Lam Chapter 6 Case Study: Identification of in vitro Metabolite/Decomposition Products of the Novel DNA Alkylating Agent Laromustine (pages 229–244): Ala F. Nassar, Jing Du, David Roberts, Kevin Lin, Mike Belcourt, Ivan King and Tukiet T. Lam Chapter 7 Strategies for the Detection of Reactive Intermediates in Drug Discovery and Development (pages 245–294): Mark P. Grillo Chapter 8 Safety Testing of Drug Metabolites: Mist Guidance Impact on the Practice of Industrial Drug Metabolism (pages 295–312): J. Greg Slatter Considerable attention has been focused recently on the potential role of human drug metabolites in drug safety and on how to provide a risk assessment for these molecules using preclinical safety models.