Biotransformation and Metabolite Elucidation of Xenobiotics

ALA F. NASSAR, PHD, has worked in the pharmaceutical industry for more than ten years. For over five years, Dr. Nassar oversaw the drug metabolism and bioanalytical department at Vion Pharmaceuticals, working in these key areas of drug discovery and development. One principal area of his research involved understanding how structure modification can improve the ADME profile for new chemical entities as they advance toward clinical candidacy. He identified and subsequently patented pharmacologically active metabolites of Nexavar (sorafenib), and recently identified the pharmacologically active metabolite of Onrigin (laromustine), and is in the process of seeking a patent on this discovery. Dr. Nassar has more than fifty publications in journal articles and book chapters; and has taught and coordinated several courses on bioanalytical chemistry, LC-MS, and drug metabolism to share his experience with other scientists in the field. Currently, he is the Director of the Mass Spectrometry Facility and Research Assistant Professor at Brandeis University.

"Contributors mostly from pharmaceutical companies provide a systematic introduction to characterizing metabolites, which has become an important element in drug discovery. They write for scientists involved in designing, developing, and advancing metabolic characterizations for drug discovery and development, and for researchers and students in fields that might call for such characterizations." (Book News Inc., February 2011)

• 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 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).INDEX.