Handbook of Pharmaceutical Analysis by HPLC (eBook)

Front Cover 1
Handbook of Pharmaceutical Analysis by HPLC 4
Copyright Page 5
Contents 6
Preface 16
Contributors 18
Chapter 1. Overview: Handbook of Pharmaceutical Analysis by HPLC 22
I. Introduction 22
II. Key Concepts in HPLC 24
III. HPLC Instrumentation in Pharmaceutical Analysis 24
IV. HPLC Columns in Pharmaceutical Analysis 25
V. Sample Preparation 25
VI. Method Development 26
VII. Method Validation 26
VIII. Ion Chromatography 27
IX. How to be More Successful with HPLC Analysis 27
X. Regulatory Practices 28
XI. HPLC System Calibration 28
XII. System Validation 29
XIII. Assay and Stability Testing 30
XIV. Impurity Evaluations 30
XV. Dissolution Testing 31
XVI. Cleaning Validation 32
XVII. High-throughput Screening 32
XVIII. Chiral Separations 33
XIX. LC-MS 34
XX. LC-NMR 35
XXI. Chromatography Data Processing 37
XXII. New Developments in HPLC 37
References 37
Chapter 2. Key Concepts of HPLC in Pharmaceutical Analysis 40
Abstract 41
I. Introduction 41
II. Fundamental Concepts 43
Ill. Mobile Phase Parameters 56
IV. Isocratic Vs. Gradient Analysis 60
V. Limit of Quantitation 64
VI. Glossary of HPLC Terms 64
VII. Summary and Conclusion 65
Acknowledgments 65
References 65
Chapter 3. HPLC Instrumentation in Pharmaceutical Analysis: Status, Advances, and Trends 68
Abstract 69
I. Introduction 69
II. HPLC Solvent Delivery Systems 71
III. Manual Injectors 79
IV. Autosamplers 80
V. Detectors 83
VI. UV/VIS Absorbance Detectors 83
VII. Photodiode Array (PDA) Detectors 86
VIII. Other Detectors 88
IX. Data Handling 90
X. Instrumental Bandwidth (IBW) 90
XI. Instrumentation Trends in Pharmaceutical Analysis 93
XII. Manufacturers 94
XIII. Summary and Conclusion 94
Acknowledgments 94
References 94
Chapter 4. HPLC Columns for Pharmaceutical Analysis 98
Abstract 98
I. Introduction 99
II. Column Physics 99
III. Column Chemistry 118
IV. Summary 140
References 141
Chapter 5. Sample Preparation for HPLC Analysis of Drug Products 144
Abstract 144
I. Introduction 145
II. Sample Preparation Overview 146
III. Primary SP Concerns for Types of Analysis 154
IV. Sample Preparation Trends in Pharmaceutical Analysis 155
V. Case Studies 156
VI. Summary and Conclusion 163
Acknowledgments 163
References 164
Chapter 6. HPLC Method Development 166
Abstract 166
I. Introduction 167
II. Phase-Appropriate Method Development 168
III. Proactive Method Development 170
IV. Development, Validation, and Use of Early Phase Methods 180
V. Final Method Development and Validation 187
VI. Conclusions 208
Acknowledgments 209
References 209
Chapter 7. Validation of HPLC Methods in Pharmaceutical Analysis 212
Abstract 213
I. Introduction 213
II. Validation Requirements for Method Type 215
III. Procedures and Protocols 217
IV. Validation Parameters 218
V. Method Validation by Phase of Development 232
VI. Reference Standards 233
VII. Method Transfer 233
VIII. Documentation 234
IX. Method Revalidation 234
X. Method-Validation Software 236
XI. Summary 237
Acknowledgments 237
References 237
Chapter 8. Ion Chromatography 240
Abstract 240
I. Introduction 240
II. Ion Chromatography Instrumentation 241
III. Chromatographic Components 242
IV. Pharmaceutical Ion Chromatography Applications 269
V. Summary and Conclusions 274
Acknowledgments 274
References 274
Chapter 9. How to Be More Successful with HPLC Analysis: Practical Aspects in HPLC Operation 276
Abstract 276
I. Introduction 277
II. Mobile Phase Preparation 277
III. HPLC Pump-operating Guides 280
IV. HPLC Column-operating Guides 280
V. Detector-operating Guides 281
VI. Autosampler-operating Guides 282
VII. Quantitation-operating Guides 283
VIII. System Shutdown-operating Guides 284
IX. Summary of HPLC Operation 284
X. Keys for Success in HPLC 284
XI. Enhancing HPLC Precision 286
XII. Conclusion and Summary 290
Acknowledgments 291
References 291
Chapter 10. Regulatory Considerations in HPLC Analysis 294
Abstract 294
I. Introduction 294
II. Chromatography—Some Generalities 295
III. Validation of Chromatographic Methods 297
IV. Impurities 307
V. Overview of Available Guidance Documents 311
VI. Conclusions 311
VII. Summary 311
Chapter 11. HPLC System Calibration for GMP Compliance 312
Abstract 312
I. Introduction 312
II. Overall Calibration Strategies 313
Ill. Calibration Procedure: A Case Study 314
IV. Overall Procedures and Documentation 320
V. Summary and Conclusion 321
Acknowledgments 322
References 322
Chapter 12. System Validation: Pre-lnstallation, IQ, OQ, and PQ 324
Abstract 324
I. Introduction: What is Validation, and Why Validate? 325
II. Timeline and Definitions 325
III. Pre-Installation 326
IV. Upon Installation 330
V. Post-Installation 344
VI. Summary 353
Acknowledgments 354
References 354
Chapter 13. Assay and Stability Testing 356
Abstract 356
I. Introduction 357
II. Stability Program in Pharmaceutical Development 359
III. Stability Testing by HPLC 367
IV. Summary and Conclusion 378
Acknowledgments 378
References 379
Chapter 14. Impurity Evaluations 380
Abstract 380
I. Introduction 380
II. Drug Substance Evaluation 384
III. Impurities in Dosage Forms 396
IV. Summary and Conclusion 398
Disclaimer 398
References 398
Chapter 15. HPLC in Dissolution Testing 400
Abstract 400
I. Introduction 401
II. Utility of HPLC Analysis in Dissolution Testing 404
Ill. Considerations of HPLC Methods in Dissolution Testing 406
IV. HPLC in Automated and Robot-Assisted Dissolution Testing 411
V. Requirements of HPLC Methods for Dissolution Testing During Drug Development Process 417
VI. Conclusion 419
Acknowledgments 420
References 420
Chapter 16. Cleaning Validation using HPLC for Analysis 422
Abstract 422
I. Introduction 422
II. Role of the Analyst 423
III. Linearity, Detection and Quantitation 424
IV. Validation of Rinse and Swabbing Procedures 425
V. Recovery Studies off Surfaces 428
VI. Verification of the Cleaning Procedure 431
VII. Verifying the Removal of Cleaning Agents 431
VIII. Conclusion 432
Acknowledgments 433
References 433
Chapter 17. LC/MS Application in High-Throughput ADME Screen 434
Abstract 434
I. Introduction 435
II. Measurement of Physicochemical Properties 436
Ill. Cytochrome P450 Inhibition Assay 445
IV. Stability 448
V. Metabolite Profiling 451
VI. Quantitative Bioanalysis 453
VII. Summary and Conclusion 459
Acknowledgments 460
References 460
Chapter 18. Chiral Separations 468
Abstract 468
I. Introduction 469
II. Separation of Enantiomers of Pharmaceutical Interest Using LC and CE 474
III. Separation of Enantiomers by Capillary Electrophoresis 478
IV. Separation of Enantiomers by Liquid Chromatography on Chiral Stationary Phases 484
V. Practical Guidelines to Chiral HPLC Separations of Pharmaceuticals 504
VI. Conclusion 509
References 510
Chapter 19. Applications of LC/MS in Pharmaceutical Analysis 520
Abstract 521
I. Introduction 521
II. LC/MS Interfaces 524
III. Mass Analyzers 535
IV. Practical Considerations in Selection of LC/MS Parameters 539
V. Peak Tracking Between LC/UV and LC/MS Methods 547
VI. Development of Generic LC/MS Method and LC/MS Database 549
VII. MS-Assisted HPLC Method Development and Validation 556
VIII. Impurity Profiling for Drug Substances and Pharmaceutical Products 562
IX. Supporting Marketed Drug Products 574
X. Conclusion 585
Acknowledgments 586
References 586
Chapter 20. Application of LC-NMR in Pharmaceutical Analysis 590
Abstract 590
I. Introduction 591
II. Instrumentation and Design 592
III. Practical Applications 594
IV. Related Hyphenated Techniques 597
V. Conclusion 599
References 599
Chapter 21. Chromatography Data Systems (CDS) in the Pharmaceutical Laboratory: Its History, Advances, and Future Direction 602
Abstract 602
I. Introduction 603
II. A Historical Look at CDS Development 603
III. Technological Advances 609
IV. Specific Needs of the Pharmaceutical Industry 623
V. Future Direction 629
Acknowledgments 630
References 630
Chapter 22. New Developments in HPLC 632
Abstract 632
I. Introduction 632
II. Simplifying Sample Preparation 633
III. New Column Technologies 635
IV. Improvements in Detectors 636
V. Improvements in HPLC Throughput 637
VI. Summary 648
Acknowledgments 649
References 649
Index 652