Separation Methods in Drug Synthesis and Purification (Handbook of Analytical Separations)

Front Cover......Page 1
Separation Methods in Drug Synthesis and Purification......Page 4
Copyright Page......Page 5
Contents......Page 14
Editor's Preface......Page 6
Series Editor's Preface......Page 10
List of Contributors......Page 12
1.1 Fundamentals of HPLC......Page 24
1.2 Chromatographic column and column packing particles......Page 31
1.3 Separation modes in HPLC......Page 36
1.4 Method development and optimisation of conditions in isocratic HPLC......Page 58
1.5 Development of gradient-elution separations......Page 72
1.7 References......Page 92
2.1 Introduction......Page 96
2.2 Theory......Page 97
2.3 Strategy for production of fast gradients......Page 98
2.4 Fast gradients in practice......Page 105
2.5 References......Page 108
3.1 Introduction to capillary electrophoresis......Page 110
3.2 Analysis of pharmaceuticals by CE......Page 112
3.3 Low-pH buffer for analysis of basic drugs......Page 113
3.4 High-pH buffer for analysis of acidic drugs......Page 115
3.5 Micellar electrokinetic chromatography (MEKC) for neutral and/or charged drugs......Page 116
3.6 Microemulsion electrokinetic chromatography (MEEKC) for neutral and/or charged drugs......Page 118
3.7 Indirect UV detection method for analysis of inorganic anions......Page 120
3.8 Indirect UV detection method for analysis of simple organic acids......Page 123
3.9 Indirect UV detection method for analysis of metal ions......Page 124
3.10 Non-aqueous CE for analysis of acidic and basic drugs......Page 125
3.11 Benefits of adopting standard CE methods......Page 126
3.12 References......Page 128
4.1 Introduction......Page 130
4.2 Basic principles of capillary electrochromatography......Page 131
4.4 Stationary phases used in CEC......Page 136
4.5 Operational characteristics of CEC......Page 140
4.6 Gradient and pressure-assisted (pseudo) CEC......Page 145
4.8 Glossary of symbols......Page 146
4.9 References......Page 147
5.1 Introduction......Page 150
5.2 LC/MS analysis of high-throughput parallel synthesis libraries......Page 153
5.3 Example for monitoring the rehearsal phase of the synthesis of a solid-phase library......Page 163
5.4 LC/UV/MS as a pre-screen for autoprep-solution phase......Page 167
5.5 Assisted automated LC/MS analysis......Page 174
5.6 The analysis of split-pool combinatorial libraries......Page 175
5.7 Conclusions and future......Page 182
5.8 References......Page 183
6.1 Introduction......Page 186
6.2 Responses and response functions......Page 188
6.3 Univariate optimization strategies......Page 193
6.4 Factorial methods......Page 195
6.5 Mixture designs......Page 220
6.6 Robustness/ruggedness......Page 224
6.7 The simplex sequential approach......Page 226
6.8 Automating the whole process: expert systems and knowledge based systems......Page 232
6.9 References......Page 233
7.1 Introduction......Page 236
7.2 The process development cycle......Page 240
7.4 Discovery experiment stage......Page 248
7.5 Development stage......Page 255
7.6 Economics......Page 266
7.7 Safety and environmental......Page 298
7.8 Regulatory and compliance......Page 305
7.9 List of symbols......Page 311
7.11 References......Page 312
8.1 Introduction......Page 316
8.2 Instrumental considerations......Page 319
8.3 Operating principles and gradient details......Page 322
8.4 A worked example......Page 323
8.5 Practical considerations and 'calibrated' methods......Page 334
8.6 Additional system developments......Page 350
8.7 Mass directed autoprep......Page 352
8.8 Conclusion......Page 358
8.10 References......Page 359
9.1 Introduction......Page 360
9.2 Direct enantioseparation by liquid chromatography with chiral stationary phases (CSPs)—chiral selectors and chiral recognition mechanisms......Page 371
9.3 Some aspects of preparative enantioseparation methods......Page 442
9.4 Other enantioselective liquid-phase separation techniques......Page 445
9.6 Addendum to literature—books on chiral discrimination......Page 448
9.7 References......Page 449
10.1 Planar chromatography......Page 462
10.2 The components of the planar stationary phase......Page 471
10.3 Mobile phases for thin-layer chromatography......Page 479
10.4 The chambers......Page 481
10.5 Detection......Page 487
10.6 Application of TLC in pharmaceutical and forensic analysis......Page 494
10.7 Quo vadis thin-layer chromatography......Page 517
10.9 References......Page 521
11.1 Introduction......Page 526
11.2 Strategy of QSRR research......Page 528
11.3 Retention prediction......Page 536
11.4 Molecular mechanism of retention in view of QSRR......Page 541
11.5 Chromatographic methods of determination of hydrophobicity......Page 545
11.6 Applications of QSRR in molecular pharmacology and rational drug design......Page 547
11.7 Concluding remarks......Page 552
11.8 References......Page 553
12.1 Introduction......Page 558
12.2 Measurements of compound lipophilicity using chromatography......Page 559
12.3 Measurements of membrane transport by immobilised artificial membrane (IAM) HPLC......Page 572
12.4 Measurements of drug–protein binding constants using chromatography......Page 575
12.5 Measurements of solubility by HPLC......Page 580
12.6 Measurements of acid–base character (pKa) by HPLC......Page 582
12.7 Measurements of H-bond acidity, basicity and polarisability–dipolarity by HPLC......Page 587
12.9 References......Page 603
Subject Index......Page 608