主题：【转帖】液质联用－－分析药物

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
v
vi CONTENTS
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
CONTENTS vii
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
viii CONTENTS
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

液质联用