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Mass Spectrometry in Drug Metabolism and Pharmacokinetics



Mass Spectrometry in Drug Metabolism and Pharmacokinetics

Ragu Ramanathan (Editor)

ISBN: 978-1-118-21157-1 September 2011 390 Pages

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This timely reference discusses mass spectrometry in drug metabolism and pharmacokinetic studies. With contributions by professionals from the pharmaceutical industry, this book begins with a review of current mass spectrometry techniques and applications, followed by discussions of various methods for using MS in drug metabolism studies and pharmacokinetics. Highlighting the critical importance of ADME studies for understanding how a drug is absorbed, distributed, metabolized, and excreted by the body, the book s focuses on the use of LC/MS and MALDI-MS. This is a valuable reference for scientists in the pharmaceutical industry, medicine, academia, and even those working in homeland defense.
Preface vii

About the Editor ix

Contributors xi

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

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

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

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

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

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

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

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

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

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

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

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

Index 383

“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)