Nassar Biotransformation and Metabolite Elucidation of Xenobiotics

Characterization and Identification
1. Auflage 2011
ISBN: 978-1-118-09777-9
Verlag: John Wiley & Sons
Format: EPUB
Kopierschutz: Adobe DRM (»Systemvoraussetzungen)

E-Book, Englisch, 328 Seiten, E-Book

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.

Autoren/Hrsg.

Nassar, Ala F.

Inhaltsverzeichnis

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.

Über Autor(innen)

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.