Page 13 - Chiral Separation Techniques

Contents XIII

11.4 Conclusions 299
References 299

12 Sub- and Supercritical Fluid Chromatography for Enatiomer
Separations 301
Karen W. Phinney

12.1 Introduction 301
12.2 Sub- and Supercritical Fluid Chromatography 302
12.2.1 Properties of Supercritical Fluids 302
12.2.2 Supercritical Fluids as Mobile Phases 303
12.2.3 Instrumentation for SFC 304
12.3 Advantages of SFC for Chiral Separations 304
12.3.1 Increased Efficiency 306
12.3.2 Rapid Method Development 307
12.3.3 Column Coupling 307
12.3.4 Preparative Separations 308
12.4 Chiral Stationary Phases in SFC 309
12.4.1 Brush-type 309
12.4.2 Cyclodextrins 310
12.4.3 Derivatized Polysaccharides 311
12.4.4 Macrocyclic Antibiotics 311
12.4.5 Other CSPs 312
12.5 Method Development in Chiral SFC 313
12.5.1 Stationary Phase Selection 313
12.5.2 Modifiers 313
12.5.3 Temperature 314
12.5.4 Pressure 314
12.5.5 Flow Rate 314
12.6 Conclusions 315
References 315

13 International Regulation of Chiral Drugs 319
Sarah K. Branch

13.1 Introduction 319
13.2 Requirements in the European Union 324
13.2.1 Introduction 324
13.2.2 Note for Guidance on Investigation of Chiral Active Substances 325
13.2.3 Chemistry and pharmacy aspects 325
13.2.3.1 Synthesis of the Active Substance 325
13.2.3.2 Quality of the Active Substance 326
13.2.4 Preclinical and Clinical Studies 328