The goal of this book is to improve the readers' knowledge ofmetabolite elucidation in drug metabolism by exposing them to indepth coverage of the biotransformation of xenobiotics, strategiesfor identifying and characterizing metabolites, FDA guidelines, andcase studies on how to improve the decision-making process instructural modification of drug candidates to reduce toxicity.The book consists of 8 chapters; it first provides anintroduction on biotransformation of xenobiotics, and then presentsmodern approaches and strategies for dealing with metabolitecharacterization, using tools such as LC-MS, H-D exchange, stableisotopes LC-MS-NMR, and radiolabeled compounds. Also, strategiesfor dealing with reactive intermediates in drug discovery anddevelopment are presented as well as case studies on improving thedecision-making process in the structural modification of drugcandidates. The last chapter discusses the regulatory perspectivesof safety testing of drug metabolites and why, how, and when totest their safety.

PREFACE.CONTRIBUTORS.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 IDENTIFICATIONIN DRUG METABOLISM (Yongmei Li).3 TOOLS OF CHOICE FOR ACCELERATING METABOLITE IDENTIFICATION:MASS SPECTROMETRY TECHNOLOGY DRIVES METABOLITE IDENTIFICATIONSTUDIES FORWARD (Ala F. Nassar).4 IMPROVING DRUG DESIGN: CONSIDERATIONS FOR THE STRUCTURALMODIFICATION PROCESS (Ala F. Nassar).5 CASE STUDY: THE UNANTICIPATED LOSS OFN2 FROM NOVEL DNA ALKYLATING AGENTLAROMUSTINE BY COLLISION-INDUCED DISSOCIATION: NOVEL REARRANGEMENTS(Ala F. Nassar, Jing Du, David Roberts, Kevin Lin, MikeBelcourt, Ivan King, and TuKiet T. Lam).6 CASE STUDY: IDENTIFICATION OF IN VITROMETABOLITE/DECOMPOSITION PRODUCTS OF THE NOVEL DNA ALKYLATING AGENTLAROMUSTINE (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 DRUGDISCOVERY AND DEVELOPMENT (Mark P. Grillo).8 SAFETY TESTING OF DRUG METABOLITES: MIST GUIDANCE IMPACT ONTHE PRACTICE OF INDUSTRIAL DRUG METABOLISM (J. GregSlatter).INDEX.