Mass Spectrometry for Drug Discovery and Drug Development (eBook)

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