Bioanalytical Separations (eBook)

Cover 1
Contents 8
Preface 6
Chapter 1. New developments in integrated sample preparation for bioanalysis 18
1.1 Introduction 18
1.2 Chromatography-based extraction techniques 21
1.3 Diffusion-based extraction techniques 33
1.4 Concluding remarks 52
1.5 Acknowledgments 55
1.6 List of abbreviations 55
1.7 References 56
Chapter 2. Solid-phase extraction on molecularly imprinted polymers 62
2.1 Introduction 62
2.2 Imprint preparation 63
2.3 MISPE method development strategies 69
2.4 Solid-phase extraction applications 72
2.5 Conclusions 85
2.6 References 86
Chapter 3. Techniques for sample preparation using solid-phase extraction 90
3.1 Introduction 90
3.2 Description of the sorbents 91
3.3 Off-line Methods 92
3.4 Cation-exchange solid phase extraction 99
3.5 Anion-exchange solid phase extraction 101
3.6 On-line methods 102
3.7 Conclusions 106
3.8 References 106
Chapter 4. Turbulent flow chromatography in bioanalysis 108
4.1 Introduction 108
4.2 Background 109
4.3 Applications of turbulent flow chromatography 128
4.4 Conclusions 144
4.5 References 144
Chapter 5. Chiral bioanalysis 146
5.1 Introduction 146
5.2 Chiral stationary phases 154
5.3 Applications of chiral HPLC in bioanalysis 164
5.4 Conclusions 197
5.5 References 197
Chapter 6. Method development in reversed-phase chromatography 202
6.1 Introduction 202
6.3 Method development strategy 217
6.4 Conclusion 230
6.5 References 231
Chapter 7. Immobilized enzyme reactors in liquid chromatography: On-line bioreactors for use in synthesis and drug discovery 232
7.1 Introduction 232
7.2 Immobilized enzymes 233
7.3 On-line immobilized enzyme reactors (IMERS) 239
7.4 Immobilized enzymes and IMERs in drug discovery 250
7.5 References 250
Chapter 8. Use of liquid chromatography-mass spectrometry in acute human toxicology 252
8.1 Introduction 252
8.2 Methodical considerations 253
8.3 Applications of LC-MS in clinical toxicological analysis 257
8.4 Conclusions and perspectives 283
8.5 Abbreviations used in the text 284
8.6 References 284
Chapter 9. HPLC-MS(MS) for bioanalysis in drug discovery and development 288
9.1 Introduction 288
9.2 The use of generic methods 289
9.3 Sample pooling and cocktail dosing 298
9.4 Short column HPLC 300
9.5 Sample introduction onto HPLC 304
9.6 The use of gradient elution with high flow rates 305
9.7 Conclusions 308
9.8 Acknowledgments 308
9.9 References 308
Chapter 10. Biomedical applications of directly-coupled chromatography-nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS) 310
10.1 Introduction 310
10.2 Technical developments in HPLC-NMR and HPLC-NMR-MS 311
10.3 Operational methods in HPLC-NMR and HPLC-NMR-MS 315
10.4 Applications in combinatorial chemistry 317
10.5 Application to drug impurities 318
10.6 Chiral HPLC-NMR and HPLC-CD for pharmaceutical mixtures 319
10.7 Application to natural products 321
10.8 Application to drug metabolism 323
10.9 Future developments 338
10.10 Conclusions 342
10.11 References 342
Chapter 11. Ultra-sensitive detection of radiolabelled drugs and their metabolites using accelerator mass spectrometry 348
11.1 Introduction 348
11.2 Instrumentation 350
11.3 Sample preparation 352
11.4 Data analysis 353
11.5 Applications 354
11.6 Limits of detection and quantification 358
11.7 Conclusions and the future 362
11.8 References 364
Chapter 12. Biomedical applications of inductively coupled plasma mass spectrometry (ICP-MS) as an element specific detector for chromatographic separations 368
12.1 An introduction to ICP-MS 368
12.2 ICP-MS as an element specific detector for chromatographic separations 376
12.3 Applications of ICP-MS in the biomedical field 379
12.4 Summary 385
12.5 References 387
12.6 Appendix 388
Chapter 13. Chromatography in a regulated environment 390
13.1 Introduction 390
13.2 Regulatory issues 392
13.3 Bioanalytical validation process 395
13.4 Study documentation 420
13.5 Statistical considerations 421
13.6 The future 423
13.7 Conclusion 424
13.8 References 425
Subject index 430