Biotransformation and Metabolite Elucidation of Xenobiotics: Characterization and Identification
DescriptionThe 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.
1 HUMAN BIOTRANSFORMATION (Andrew Parkinson, Brian W. Ogilvie, Brandy L. Paris, Tiffi ni N. Hensley, and Greg J. Loewen).
2 ANALYTICAL TOOLS AND APPROACHES FOR METABOLITE IDENTIFICATION IN DRUG METABOLISM (Yongmei Li).
3 TOOLS OF CHOICE FOR ACCELERATING METABOLITE IDENTIFICATION: MASS SPECTROMETRY TECHNOLOGY DRIVES METABOLITE IDENTIFICATION STUDIES FORWARD (Ala F. Nassar).
4 IMPROVING DRUG DESIGN: CONSIDERATIONS FOR THE STRUCTURAL MODIFICATION PROCESS (Ala F. Nassar).
5 CASE STUDY: THE UNANTICIPATED LOSS OF N2 FROM NOVEL DNA ALKYLATING AGENT LAROMUSTINE BY COLLISION-INDUCED DISSOCIATION: NOVEL REARRANGEMENTS (Ala F. Nassar, Jing Du, David Roberts, Kevin Lin, Mike Belcourt, Ivan King, and TuKiet T. Lam).
6 CASE STUDY: IDENTIFICATION OF IN VITRO METABOLITE/DECOMPOSITION PRODUCTS OF THE NOVEL DNA ALKYLATING AGENT LAROMUSTINE (Ala F. Nassar, Jing Du, David Roberts, Kevin Lin, Mike Belcourt, Ivan King, and TuKiet T. Lam).
7 STRATEGIES FOR THE DETECTION OF REACTIVE INTERMEDIATES IN DRUG DISCOVERY AND DEVELOPMENT (Mark P. Grillo).
8 SAFETY TESTING OF DRUG METABOLITES: MIST GUIDANCE IMPACT ON THE PRACTICE OF INDUSTRIAL DRUG METABOLISM (J. Greg Slatter).