Biotransformation and Metabolite Elucidation of Xenobiotics

Characterization and Identification
1. Auflage 2010
ISBN: 978-0-470-50478-9
Verlag: Wiley

Buch, Englisch, 344 Seiten, Format (B × H): 161 mm x 240 mm, Gewicht: 680 g

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.

Autoren/Hrsg.

Nassar, Ala F

Fachgebiete

• Naturwissenschaften Chemie Analytische Chemie Magnetresonanz
• Naturwissenschaften Chemie Organische Chemie Biochemie
• Naturwissenschaften Chemie Analytische Chemie Massenspektrometrie, Spektroskopie, Spektrochemie

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 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.

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.