《LC/MS APPLICATIONS IN DRUG DEVELOPMENT》液质联用在医学上的应用
Wiley-Interscience Series on Mass Spectrometry
Series Editors
Dominic M. Desiderio
Departments of Neurology and Biochemistry
University of Tennessee Health Science Center
Nico M. M. Nibbering
University of Amsterdam
The aim of the series is to provide books written by experts in the various
disciplines of mass spectrometry, including but not limited to basic and
fundamental research, instrument and methodological developments, and
applied research.
Books in the Series
Michael Kinter, Protein Sequencing and Identification Using Tandem Mass
Spectrometry 0-471-32249-0
Mike S. Lee, LC/MS Applications in Drug Development 0-471-40520-5
Forthcoming Books in the Series
Chhabil Dass, Principles and Practice of Biological Mass Spectrometry
0-471-33053-1
CONTENTS
Preface 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
请点击此处下载
收藏
