ABSTRACT
Abstract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 213 4.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 214 4.2 Fundamental Considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 215
4.2.1 Effect of Efficiency, Selectivity, and Retention on Separation Time . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 215
4.2.2 SFC vs. LC. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 216 4.2.3 SFC vs. GC . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 220
4.3 Effect of Chiral Stationary Phases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 221 4.4 Effect of Modifiers and Additives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 225 4.5 Thermodynamic Aspects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 228 4.6 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 230 Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 231 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 231
60252: “60252_c004” — 2007/9/17 — 19:14 — page 214 — #2
There is an increasing demand for simple and fast analytical methods for enantiomers. Today, the pharmaceutical industry is facing the major challenges of shortening drug discovery and development cycle time to push new drug candidates into the market [1-4]. Various new technologies have been utilized to increase the speed and improve the efficiency of drug discovery and development [2, 4]. Accordingly, the most urgent goal for analytical scientists is to minimize assay time and maximize analytical information using newly developed technologies [5-8]. Nearly 60-70 % of the most frequently prescribed drugs and the drug candidates that entered the development process in the United States are single enantiomers [9, 10]. To ensure the efficacy and safety of currently used and newly developed drugs, it is important to isolate the enantiomers and to examine each one separately [11]. Furthermore, it is necessary to check the chiral purity of drug raw materials and to monitor the stereochemical composition of drugs during development, manufacturing, and storage. Conventional synthese and modern combinatorial libraries used in drug discovery and development require high-throughput screening methods to handle the large number of samples [13-15].
