Mass Spectrometry in Drug Metabolism and Pharmacokinetics

by Ragu Ramanathan (Editor)

Overview

Inside this book are a host of practical tools and techniques that enable you to fully leverage the capabilities of mass spectrometry in order to get the most out of drug metabolism and pharmacokinetics studies. You'll learn the latest applications for determining how a drug is absorbed, distributed, metabolized, and excreted by the body.

Product Details

ISBN-13:	9781118211571
Publisher:	Wiley
Publication date:	09/20/2011
Sold by:	JOHN WILEY & SONS
Format:	eBook
Pages:	408
File size:	6 MB

About the Author

Ragu Ramanathan received a B.Sc. in Chemistry from the University of Southern Mississippi and a Ph.D. in Physical Chemistry/Mass Spectrometry from the University of Florida. His graduate research focused on coupling of electrospray ionization (ESI) to Fourier transform ion cyclotron resonance (FTICR) mass spectrometer. After spending three years as a postdoctoral research fellow with Professor Michael L. Gross at the Washington University, St. Louis, Missouri, Dr. Ramanathan managed the Center for Advanced Mass Spectrometry at the Analytical Bio-Chemistry Laboratories, Columbia, Missouri. In 1998, Dr. Ramanathan joined Schering-Plough Research Institute’s (SPRI) Drug Metabolism and Pharmacokinetics (DMPK) Department and completed his tenure as a senior principal scientist in 2008. While at SPRI, Dr. Ramanathan was involved in the application of LC–MS for profiling and characterization of metabolites of drug candidates in the preclinical development and clinical stages. Dr. Ramanathan was with Pfizer Global Research and Development from 1999 to 2002 as a group leader of the Ann Arbor site biotransformation group. Dr. Ramanathan is currently an associate director at the Bristol-Myers Squibb, Co. and is responsible for elucidating biotransformation pathways of development drug candidates. Dr. Ramanathan’s accomplishments include 35 peer-reviewed papers, 10 book chapters, and over 60 oral/poster presentations. He also served as a chairperson for the North Jersey ACS Mass Spectrometry Discussion Group and as a chairman for DMPK sessions of the American Society for Mass Spectrometry and Eastern Analytical Symposium meetings.

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Table of Contents

Preface vii

About the Editor ix

Contributors xi

1 Evolving Role of Mass Spectrometry in Drug Discovery and Development Dil M. Ramanathan Richard M. LeLacheur 1

2 Quantitative Bioanalysis in Drug Discovery and Development: Principles and Applications Ayman El-Kattan Chris Holliman Lucinda H. Cohen 87

3 Quadrupole, Triple-Quadrupole, and Hybrid Linear Ion Trap Mass Spectrometers for Metabolite Analysis Elliott B. Jones 123

4 Applications of Quadrupole Time-of-Flight Mass Spectrometry in Reactive Metabolite Screening Jose M. Castro-Perez 159

5 Changing Role of FTMS in Drug Metabolism Petia A. Shipkova Jonathan L. Josephs Mark Sanders 191

6 High-Resolution LC-MS-Based Mass Defect Filter Approach: Basic Concept and Application in Metabolite Detection Haiying Zhang Donglu Zhang Mingshe Zhu Kenneth L. Ray 223

7 Applications of High-Sensitivity Mass Spectrometry and Radioactivity Detection Techniques in Drug Metabolism Studies Wing W. Lam Cho-Ming Loi Angus Nedderman Don Walker 253

8 Online Electrochemical-LC-MS Techniques for Profiling and Characterizing Metabolites and Degradants Paul H. Gamache David F. Meyer Michael C. Granger Ian N. Acworth 275

9 LC-MS Methods with Hydrogen/Deuterium Exchange for Identification of Hydroxylamine, N-Oxide, and Hydroxylated Analogs of Desloratadine Natalia A. Penner Joanna Zgoda-Pols Ragu Ramanathan Swapan K. Chowdhury Kevin B. Alton 295

10 Turbulent-Flow LC-MS: Applications for Accelerating Pharmacokinetic Profiling and Metabolite Identification Joseph L. Herman Joseph M. Di Bussolo 311

11 Desorption Ionization Techniques for Quantitative Analysis of Drug Molecules Jason S. Gobey John Janiszewski Mark J. Cole 341

12MALDI Imaging Mass Spectrometry for Direct Tissue Analysis of Pharmaceuticals Yunsheng Hsieh Walter A. Korfmacher 359

Index 383

What People are Saying About This

From the Publisher

“All in all, the book delivers on its promises to introduce and review the current art of mass spectrometry for the related disciplines of drug metabolism and pharmacokinetics. I highly recommend it.” (JACS Book Reviews, June 2009)

“In comparison to other books on mass spectrometry, this one not only provides both the basic and latest knowledge in mass spectrometry, but integrates the theory with applications to drug metabolism and pharmacokinetics.” (Doody's, April 2009)

"Mass Spectrometry in Drug Metabolism and Pharmacokinetics is a valuable and interesting resource for a broad readership, including scientists starting to work in DMPK as well as undergraduate and graduate students getting involved in drug discovery and characterization by means of MS. A wealth of information is provided and all of the contributing authors have done an excellent job in explaining and outlining particular aspects of MS-based tools in DMPK ... the book is highly recommended reading." (Journal of the American Society for Mass Spectrometry, March 2009)

Editorial Reviews

Reviewer: Xiaochao Ma, PhD (University of Kansas Medical Center)
Description: This practical book covers the latest applications of mass spectrometry in drug absorption, distribution, metabolism, and excretion. The authors are experts in the fields of drug metabolism and pharmacokinetics from pharmaceutical companies, instrumental corporations, and universities.
Purpose: The purpose is to provide comprehensive information about mass spectrometry for solving complex problems in chemical analysis.
Audience: This book is valuable for scientists working in academic, industrial, and healthcare-related fields, who use mass spectrometry to investigate drug metabolism and pharmacokinetics, chemical markers of toxicity and disease, xenobiotic exposure, and so on.
Features: The 12 chapters can be characterized in one of three ways: 1) introducing the knowledge of mass spectrometry from the simple basics to the complex applications; 2) combining mass spectrometry techniques with the applications in drug metabolism and pharmacokinetics; 3) sharing of first-hand laboratory experience from leading experts around the world. The book begins with an overview of mass spectrometry in drug discovery and development and then details the applications of mass spectrometry in metabolites screening, identification, and quantification.
Assessment: In comparison to other books on mass spectrometry, this one not only provides both the basic and latest knowledge in mass spectrometry, but integrates the theory with applications to drug metabolism and pharmacokinetics. For instance, chapter 4, on the applications of quandrupole time-of- flight (Q-TOF) mass spectrometry in reactive metabolites screening, demonstrates the importance of exact mass measurements and high-resolution mass spectrometry in metabolites screening and identification. This chapter also introduces the MetaboLynx software, which could facilitate the identification of metabolites. This knowledge is very helpful for scientists in the metabolomic field.

Doody's Review Service

All in all, the book delivers on its promises to introduce and review the current art of mass spectrometry for the related disciplines of drug metabolism and pharmacokinetics. I highly recommend it.” (JACS Book Reviews, June 2009)

“In comparison to other books on mass spectrometry, this one not only provides both the basic and latest knowledge in mass spectrometry, but integrates the theory with applications to drug metabolism and pharmacokinetics.” (Doody's, April 2009)

"Mass Spectrometry in Drug Metabolism and Pharmacokinetics is a valuable and interesting resource for a broad readership, including scientists starting to work in DMPK as well as undergraduate and graduate students getting involved in drug discovery and characterization by means of MS. A wealth of information is provided and all of the contributing authors have done an excellent job in explaining and outlining particular aspects of MS-based tools in DMPK ... the book is highly recommended reading." (Journal of the American Society for Mass Spectrometry, March 2009)

From the Publisher