Mass Spectrometry for Drug Discovery and Drug Development

WALTER A. KORFMACHER, PhD, is Director of Bioanalysis at Genzyme, a Sanofi company, and Associate Editor at the Journal of Mass Spectrometry. Previously, he held positions at the FDA's National Center for Toxicological Research, Schering-Plough Research Institute, Merck Research Laboratories, and Medpace Bioanalytical Laboratories. Dr. Korfmacher is an international leader in developing mass spectrometry techniques and strategies for new drug discovery and drug metabolism applications. A 2009 recipient of the CPSA Distinguished Analytical Scientist Award, he has published more than 150 articles in the scientific literature and made more than eighty presentations at various scientific forums.

Contributors ix

Preface xi

1 Overview of the Various Types of Mass Spectrometers that are Used in Drug Discovery and Drug Development 1
Gérard Hopfgartner

2 Utility of High-Resolution Mass Spectrometry for New Drug Discovery Applications 37
William Bart Emary and Nanyan Rena Zhang

3 Quantitative Mass Spectrometry Considerations in a Regulated Environment 55
Mohammed Jemal and Yuan-Qing Xia

4 Mass Spectrometry for Quantitative In Vitro ADME Assays 97
Jun Zhang and Wilson Z. Shou

5 Metabolite Identifi cation Using Mass Spectrometry in Drug Development 115
Natalia Penner, Joanna Zgoda-Pols, and Chandra Prakash

6 MS Analysis of Biological Drugs, Proteins, and Peptides 149
Yi Du, John Mehl, and Pavlo Pristatsky

7 Characterization of Impurities and Degradation Products in Small Molecule Pharmaceuticals and Biologics 191
Hui Wei, Guodong Chen, and Adrienne A. Tymiak

8 Liquid Extraction Surface Analysis (LESA): A New Mass Spectrometry-Based Technique for Ambient Surface Profiling 221
Daniel Eikel and Jack D. Henion

9 MS Applications in Support of Medicinal Chemistry Sciences 239
Maarten Honing, Benno Ingelse, and Birendra N. Pramanik

10 Imaging Mass Spectrometry of Proteins and Peptides 277
Michelle L. Reyzer and Richard M. Caprioli

11 Imaging Mass Spectrometry for Drugs and Metabolites 303
Stacey R. Oppenheimer

12 Screening Reactive Metabolites: Role of Liquid Chromatography–High-Resolution Mass Spectrometry in Combination with “Intelligent” Data Mining Tools 339
Shuguang Ma and Swapan K. Chowdhury

13 Mass Spectrometry of siRNA 357
Mark T. Cancilla and W. Michael Flanagan

14 Mass Spectrometry for Metabolomics 387
Petia Shipkova and Michael D. Reily

15 Quantitative Analysis of Peptides with Mass Spectrometry: Selected Reaction Monitoring or High-Resolution Full Scan? 403
Lieve Dillen and Filip Cuyckens

Index 427