Mass Spectrometry in Drug Metabolism and Pharmacokinetics (eBook)

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.

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)