HPLC method development for pharmaceuticals /
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作 者：edited by Satinder Ahuja, Henrik Rasmussen.
分类号：
ISBN：9780123705402
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简介
High pressure, or high performance, liquid chromatography (HPLC) is the method of choice for checking purity of new drug candidates, monitoring changes during scale up or revision of synthetic procedures, evaluating new formulations, and running control/assurance of the final drug product. HPLC Method Development for Pharmaceuticals provides an extensive overview of modern HPLC method development that addresses these unique concerns. Includesa review and update of the current state of the art and science of HPLC, including theory, modes of HPLC, column chemistry, retention mechanisms, chiral separations, modern instrumentation (including ultrahigh-pressure systems), and sample preparation. Emphasis has been placedon implementation in a pharmaceutical setting and on providing a practical perspective. HPLC Method Developmentfor Pharmaceuticals is intended to be particularly useful for both novice and experienced HPLC method development chemists in the pharmaceutical industry and for managers who are seeking to update their knowledge. * Covers the requirements for HPLC in a pharmaceutical setting including strategies for software and hardware validation to allow for use in a regulated laboratory * Provides an overview of the pharmaceutical development process (clinical phases, chemical and pharmaceutical development activities) * Discusses how HPLC is used in each phase of pharmaceutical development and how methods are developed to support activities in each phase.
目录
Preface p. xiii
Contributors p. xv
1 Overview of HPLC Method Development for Pharmaceuticals Satinder Ahuja
I Introduction p. 1
II Theoretical Considerations p. 2
III HPLC Columns and Column Packings p. 2
IV Column Selection p. 3
V Chiral Separations p. 3
VI Contemporary HPLC p. 4
VII Hyphenated Methods p. 5
VIII Sample Preparation p. 5
IX Instrument Qualification and Software Validation p. 6
X Pharmaceutical Development p. 6
XI Drug Discovery p. 7
XII Early Phase Method Development p. 8
XIII Late Phase Development p. 8
XIV In-Process Testing p. 9
XV Method Development for Biomolecules p. 9
XVI Method Validation p. 10
XVII Troubleshooting p. 10
XVIII Molecularly Imprinted Polymers p. 10
References p. 11
2 HPLC Theory Y.V. Kazakevich
Abstract p. 13
I Introduction p. 13
II Basic Chromatographic Descriptors p. 14
III Efficiency p. 15
IV Resolution p. 20
V Main Components of the Retention Mechanism p. 22
VI General Column Mass Balance p. 24
VII Partitioning Model p. 27
VIII Adsorption Model p. 28
IX Void Volume Considerations p. 29
X Thermodynamic Relationships p. 31
XI Secondary Equilibria p. 35
XII Salt Effect p. 37
XIII Effect of Different Counteranions p. 38
XIV Inclusion of Secondary Equilibria in the Mass Balance p. 40
XV Conclusions p. 43
References p. 43
3 HPLC Columns and Packings Uwe D. Neue and Bonnie A. Alden and Edward R. Grover and Eric S. Grumbach and Pamela C. Iraneta and Alberto Mendez
Abstract p. 45
I Introduction p. 46
II Column Chemistry p. 47
III Speed and Resolution p. 68
IV Specialty Columns from Nanobore to Preparative Chromatography p. 77
V Summary p. 80
References p. 80
4 Column Characterization and Selection Dora Visky
Abstract p. 85
I Introduction p. 86
II Characteristics of RP-HPLC Columns and Chromatographic Tests p. 90
III Column Classification and Selection p. 101
IV Conclusions p. 104
Acknowledgment p. 105
References p. 105
5 Chiral Separations Xiande Wang and Weiyong Li and Henrik Rasmussen
Abstract p. 111
I Introduction p. 112
II Separation of Enantiomers on HPLC Chiral Stationary Phases p. 115
III Practical Guidelines to Chiral HPLC of Pharmaceuticals p. 135
IV Conclusions p. 137
References p. 138
6 Contemporary Liquid Chromatographic Systems for Method Development Michael E. Swartz
Abstract p. 145
I Introduction p. 146
II Traditional Instrumentation for HPLC Method Development p. 147
III Contemporary Method Development Systems p. 153
IV Migrating Methods from HPLC to UPLC p. 169
V UPLC Applications in Pharmaceutical Analysis p. 174
VI Summary and Conclusions p. 183
Acknowledgments p. 184
References p. 185
Further Reading p. 186
7 Hyphenated Techniques Daniel L. Norwood and James O. Mullis and Thomas N. Feinberg
Abstract p. 189
I Introduction and Background p. 190
II Combined Liquid Chromatography/Mass Spectrometry p. 191
III Combined Liquid Chromatography/Nuclear Magnetic Resonance Spectroscopy p. 218
V Conclusions p. 231
Acknowledgments p. 231
References p. 232
8 HPLC Sample Preparation Gregory C. Slack and Nicholas H. Snow
Abstract p. 237
I Introduction p. 238
II Fundamentals of Extraction and Chemical Equilibrium p. 239
III Choice of Samples Preparation p. 245
IV Direct Injection p. 246
V Liquid-Liquid Extraction p. 247
VI Solid-Phase Extraction p. 248
VII Solid Samples p. 254
VIII Additional Sample Preparation Methods p. 256
IX Conclusions p. 263
References p. 263
9 Instrument Qualification and Software Validation Dave van Geel
Abstract p. 270
I Introduction p. 270
II Definitions p. 271
III Qualification Model p. 278
IV Discussion: Case Study HPLC p. 291
V Summary and Conclusions p. 294
Acknowledgments p. 295
References p. 295
10 Pharmaceutical Development: From Pre-Clinical to Post Approval Kevin C. Bynum
Abstract p. 297
I Introduction p. 298
II The Role of HPLC in Drug Discovery p. 300
III The Role of HPLC in Pre-clinical Development p. 303
IV The Role of HPLC in Clinical Development p. 307
V Post Approval p. 312
VI Conclusions p. 315
References p. 315
11 HPLC Method Development for Drug Discovery LC-MS Assays in Rapid PK Applications Xiaoying Xu
Abstract p. 318
I Introduction p. 318
II Tandem MS Selected Reaction Monitoring (SRM) Development p. 319
III HPLC Method Development p. 322
IV Sample Preparation p. 324
V Matrix Effects p. 329
VI Background Interference: Enhanced Mass Resolution Strategy p. 334
VII Limit of Quantitation, Dynamic Range and Linearity p. 340
VIII Assay Samples and Generate Pharmacokinetic Reports p. 344
IX Conclusions p. 345
Acknowledgment p. 345
References p. 345
12 HPLC Method Development in Early Phase Pharmaceutical Development Henrik T. Rasmussen and Kelly A. Swinney and Sheetal Gaiki
Abstract p. 353
I Introduction p. 354
II Forced Decomposition and Impurity Profiling p. 355
III Orthogonal Screening p. 357
IV Method Selection and Optimization p. 362
V Additional Methods p. 366
VI Setting the Stage for Late Phase HPLC Method Developments p. 367
VII Conclusions p. 369
Acknowledgments p. 369
References p. 369
13 HPLC Method Development in Late Phase Pharmaceutical Development M. Ilias Jimidar and Maurits de Smet
Abstract p. 373
I Introduction p. 374
II Goals of Development p. 375
III Planning Phase p. 377
IV Method Development Phase p. 382
V Method Evaluation Phase p. 394
VI Method Transfer Phase p. 398
VII Method Performance Monitoring and Feedback p. 400
VIII Method Development Cycle Times and Documentation p. 403
IX Conclusions p. 403
References p. 404
14 Use of HPLC for In-process Testing Christine F. Richardson
Abstract p. 407
I Introduction p. 407
II Various Examples of In-Process Testing in Drug Substance Development p. 409
III Fast HPLC p. 419
IV In-Process Testing in Chemical Production p. 420
V In-Process Testing in Pharmaceutical Production p. 422
VI Conclusions and Future Directions p. 423
Acknowledgments p. 423
References p. 423
15 Method Development for Biomolecules Julee L. Driver and Douglas E. Raynie
Abstract p. 425
I Introduction p. 426
II Protein and Peptide Separations by HPLC p. 430
III Case Studies p. 434
IV Summary and Conclusions p. 437
Abbreviations p. 438
References p. 438
16 Method Validation M. Ilias Jimidar and Patrick Heylen and Maurits De Smet
Abstract p. 441
I Introduction p. 442
II Validation Process p. 444
III Validation Characteristics p. 444
IV Additional Validation Characteristics p. 450
V Robustness Testing p. 452
VI Conclusions p. 457
References p. 457
17 Troubleshooting in High Performance Liquid Chromatography Harold McNair and Lee N. Polite
Abstract p. 459
I Introduction p. 460
II Problems Observed in Chromatograms p. 460
III Operating Parameters p. 468
IV Leaks p. 472
V Pressure Problems p. 474
VI Troubleshooting Action Plan p. 475
VII Conclusions p. 477
References p. 477
Internet Resources p. 477
18 Molecularly Imprinted Polymers as Sorbents for Separations and Extractions Myra T. Koesdjojo and Yolanda H. Tennico and Vincent T. Remcho
Abstract p. 479
I Introduction p. 479
II MIP Theory p. 481
III Synthesis p. 487
IV Use of Imprinted Polymers in Separation Science p. 491
V Pharmaceutical Application for MIPs p. 493
VI Pros and Cons of MIP Sorbents p. 495
VII Conclusions and Future Outlook p. 496
References p. 497
Contributors p. xv
1 Overview of HPLC Method Development for Pharmaceuticals Satinder Ahuja
I Introduction p. 1
II Theoretical Considerations p. 2
III HPLC Columns and Column Packings p. 2
IV Column Selection p. 3
V Chiral Separations p. 3
VI Contemporary HPLC p. 4
VII Hyphenated Methods p. 5
VIII Sample Preparation p. 5
IX Instrument Qualification and Software Validation p. 6
X Pharmaceutical Development p. 6
XI Drug Discovery p. 7
XII Early Phase Method Development p. 8
XIII Late Phase Development p. 8
XIV In-Process Testing p. 9
XV Method Development for Biomolecules p. 9
XVI Method Validation p. 10
XVII Troubleshooting p. 10
XVIII Molecularly Imprinted Polymers p. 10
References p. 11
2 HPLC Theory Y.V. Kazakevich
Abstract p. 13
I Introduction p. 13
II Basic Chromatographic Descriptors p. 14
III Efficiency p. 15
IV Resolution p. 20
V Main Components of the Retention Mechanism p. 22
VI General Column Mass Balance p. 24
VII Partitioning Model p. 27
VIII Adsorption Model p. 28
IX Void Volume Considerations p. 29
X Thermodynamic Relationships p. 31
XI Secondary Equilibria p. 35
XII Salt Effect p. 37
XIII Effect of Different Counteranions p. 38
XIV Inclusion of Secondary Equilibria in the Mass Balance p. 40
XV Conclusions p. 43
References p. 43
3 HPLC Columns and Packings Uwe D. Neue and Bonnie A. Alden and Edward R. Grover and Eric S. Grumbach and Pamela C. Iraneta and Alberto Mendez
Abstract p. 45
I Introduction p. 46
II Column Chemistry p. 47
III Speed and Resolution p. 68
IV Specialty Columns from Nanobore to Preparative Chromatography p. 77
V Summary p. 80
References p. 80
4 Column Characterization and Selection Dora Visky
Abstract p. 85
I Introduction p. 86
II Characteristics of RP-HPLC Columns and Chromatographic Tests p. 90
III Column Classification and Selection p. 101
IV Conclusions p. 104
Acknowledgment p. 105
References p. 105
5 Chiral Separations Xiande Wang and Weiyong Li and Henrik Rasmussen
Abstract p. 111
I Introduction p. 112
II Separation of Enantiomers on HPLC Chiral Stationary Phases p. 115
III Practical Guidelines to Chiral HPLC of Pharmaceuticals p. 135
IV Conclusions p. 137
References p. 138
6 Contemporary Liquid Chromatographic Systems for Method Development Michael E. Swartz
Abstract p. 145
I Introduction p. 146
II Traditional Instrumentation for HPLC Method Development p. 147
III Contemporary Method Development Systems p. 153
IV Migrating Methods from HPLC to UPLC p. 169
V UPLC Applications in Pharmaceutical Analysis p. 174
VI Summary and Conclusions p. 183
Acknowledgments p. 184
References p. 185
Further Reading p. 186
7 Hyphenated Techniques Daniel L. Norwood and James O. Mullis and Thomas N. Feinberg
Abstract p. 189
I Introduction and Background p. 190
II Combined Liquid Chromatography/Mass Spectrometry p. 191
III Combined Liquid Chromatography/Nuclear Magnetic Resonance Spectroscopy p. 218
V Conclusions p. 231
Acknowledgments p. 231
References p. 232
8 HPLC Sample Preparation Gregory C. Slack and Nicholas H. Snow
Abstract p. 237
I Introduction p. 238
II Fundamentals of Extraction and Chemical Equilibrium p. 239
III Choice of Samples Preparation p. 245
IV Direct Injection p. 246
V Liquid-Liquid Extraction p. 247
VI Solid-Phase Extraction p. 248
VII Solid Samples p. 254
VIII Additional Sample Preparation Methods p. 256
IX Conclusions p. 263
References p. 263
9 Instrument Qualification and Software Validation Dave van Geel
Abstract p. 270
I Introduction p. 270
II Definitions p. 271
III Qualification Model p. 278
IV Discussion: Case Study HPLC p. 291
V Summary and Conclusions p. 294
Acknowledgments p. 295
References p. 295
10 Pharmaceutical Development: From Pre-Clinical to Post Approval Kevin C. Bynum
Abstract p. 297
I Introduction p. 298
II The Role of HPLC in Drug Discovery p. 300
III The Role of HPLC in Pre-clinical Development p. 303
IV The Role of HPLC in Clinical Development p. 307
V Post Approval p. 312
VI Conclusions p. 315
References p. 315
11 HPLC Method Development for Drug Discovery LC-MS Assays in Rapid PK Applications Xiaoying Xu
Abstract p. 318
I Introduction p. 318
II Tandem MS Selected Reaction Monitoring (SRM) Development p. 319
III HPLC Method Development p. 322
IV Sample Preparation p. 324
V Matrix Effects p. 329
VI Background Interference: Enhanced Mass Resolution Strategy p. 334
VII Limit of Quantitation, Dynamic Range and Linearity p. 340
VIII Assay Samples and Generate Pharmacokinetic Reports p. 344
IX Conclusions p. 345
Acknowledgment p. 345
References p. 345
12 HPLC Method Development in Early Phase Pharmaceutical Development Henrik T. Rasmussen and Kelly A. Swinney and Sheetal Gaiki
Abstract p. 353
I Introduction p. 354
II Forced Decomposition and Impurity Profiling p. 355
III Orthogonal Screening p. 357
IV Method Selection and Optimization p. 362
V Additional Methods p. 366
VI Setting the Stage for Late Phase HPLC Method Developments p. 367
VII Conclusions p. 369
Acknowledgments p. 369
References p. 369
13 HPLC Method Development in Late Phase Pharmaceutical Development M. Ilias Jimidar and Maurits de Smet
Abstract p. 373
I Introduction p. 374
II Goals of Development p. 375
III Planning Phase p. 377
IV Method Development Phase p. 382
V Method Evaluation Phase p. 394
VI Method Transfer Phase p. 398
VII Method Performance Monitoring and Feedback p. 400
VIII Method Development Cycle Times and Documentation p. 403
IX Conclusions p. 403
References p. 404
14 Use of HPLC for In-process Testing Christine F. Richardson
Abstract p. 407
I Introduction p. 407
II Various Examples of In-Process Testing in Drug Substance Development p. 409
III Fast HPLC p. 419
IV In-Process Testing in Chemical Production p. 420
V In-Process Testing in Pharmaceutical Production p. 422
VI Conclusions and Future Directions p. 423
Acknowledgments p. 423
References p. 423
15 Method Development for Biomolecules Julee L. Driver and Douglas E. Raynie
Abstract p. 425
I Introduction p. 426
II Protein and Peptide Separations by HPLC p. 430
III Case Studies p. 434
IV Summary and Conclusions p. 437
Abbreviations p. 438
References p. 438
16 Method Validation M. Ilias Jimidar and Patrick Heylen and Maurits De Smet
Abstract p. 441
I Introduction p. 442
II Validation Process p. 444
III Validation Characteristics p. 444
IV Additional Validation Characteristics p. 450
V Robustness Testing p. 452
VI Conclusions p. 457
References p. 457
17 Troubleshooting in High Performance Liquid Chromatography Harold McNair and Lee N. Polite
Abstract p. 459
I Introduction p. 460
II Problems Observed in Chromatograms p. 460
III Operating Parameters p. 468
IV Leaks p. 472
V Pressure Problems p. 474
VI Troubleshooting Action Plan p. 475
VII Conclusions p. 477
References p. 477
Internet Resources p. 477
18 Molecularly Imprinted Polymers as Sorbents for Separations and Extractions Myra T. Koesdjojo and Yolanda H. Tennico and Vincent T. Remcho
Abstract p. 479
I Introduction p. 479
II MIP Theory p. 481
III Synthesis p. 487
IV Use of Imprinted Polymers in Separation Science p. 491
V Pharmaceutical Application for MIPs p. 493
VI Pros and Cons of MIP Sorbents p. 495
VII Conclusions and Future Outlook p. 496
References p. 497
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