Description
Book SynopsisIn the arena of new drug development, the rate of sample generation far exceeds the rate of sample analysis. LC/MS is an analytical tool that helps the researcher select the most promising sample for scrutiny, accelerating the discovery of new drugs. This book is the first to describe in detail the procedures and benefits of LC/MS applications.
Trade Review"…a comprehensive primer and will appeal to laboratory scientists and instructors in the pharmaceutical field…" (
Analytical Chemistry, November 2002)
"...describes...applications in each phase of drug development...provides perspective on changes in strategies for pharmaceutical analysis..." (SciTech Book News, Vol. 26, No. 2, June 2002)
"...useful not only for students and scholars of analytical chemistry, but also for managers and other scientists...another fine addition to the Wiley-InterScience Series on Mass Spectrometry, it should be in the collections of all research libraries." (The Chemist, Summer 2003)
Table of ContentsPreface ix
Acknowledgments xi
1. Introduction 1
Emerging Analytical Needs 1
Integration of LC/MS into Drug Development 3
Partnerships and Acceptance 6
Overview 10
2. Drug Development Overview 11
Analysis Perspectives 11
The Four Stages of Drug Development 12
Drug Discovery 14
Preclinical Development 15
Clinical Development 16
Manufacturing 17
3. Accelerated Drug Development 19
Accelerated Development Strategies 20
Quantitative and Qualitative Process Elements 20
Quantitative Process Pipeline 24
Qualitative Process Pipeline 25
Motivating Factors 27
Analysis Opportunities for Accelerated Development 28
Full-Time Equivalent 28
Sample Throughput Model 29
Elimination Model 29
Rate-Determining Event Model 31
Accelerated Development Perspectives 33
4. LC/MS Development 34
The Elements of LC/MS Application 34
HPLC 35
Mass Spectrometry 35
LC/MS Interface 36
LC/MS Growth 38
5. Strategies 41
Standard Methods 43
Template Structure Identification 46
Databases 49
Screening 50
Integration 53
Miniaturization 55
Parallel Processing 56
Visualization 58
Automation 61
Summary 63
6. LC/MS Applications 65
Drug Discovery 65
Proteomics 68
Protein Expression Profiling 70
Quantitation 76
Glycoprotein Mapping 78
Natural Products Dereplication 83
Lead Identification Screening 88
Bioaffinity Screening 89
Combinatorial Library Screening 92
Open-Access LC/MS 96
Structure Confirmation 97
High Throughput 100
Purification 102
Combinatorial Mixture Screening 103
In Vivo Drug Screening 106
Pharmacokinetics 109
In Vitro Drug Screening 115
Metabolic Stability Screening 118
Membrane Permeability 119
Drug-Drug Interaction 121
Metabolite Identification 122
Preclinical Development 123
Metabolite Identification 125
Impurity Identification 132
Degradant Identification 140
Clinical Development 145
Quantitative Bioanalysis—Selected Ion Monitoring 148
Quantitative Bioanalysis—Selected Reaction Monitoring 152
Quantitative Bioanalysis—Automated Solid-Phase Extraction 156
Quantitative Bioanalysis—Automated On-Line Extraction 162
Metabolite Identification 165
Degradant Identification 168
Manufacturing 171
Impurity Identification Using Data-Dependent Analysis 173
Peptide Mapping in Quality Control 176
Patent Protection 178
7. Future Applications and Prospects 183
Workstations 183
Multidimensional Analysis 186
Miniaturization 187
Information Management 189
Strategic Outsourcing 190
Summary 191
8. Perspectives on the Future Growth of LC/MS 192
9. Conclusions 195
Glossary 197
References 205
Index 235
