Chiral separations by cyclodextrin-modified capillary electrophoresis - Determination of the enantiomeric excess

Abstract

The chiral nature of living systems has strong implications for biologically active compounds interacting with them. Consequently, the stereoisomers of drugs can differ in both pharmacodynamic and pharmacokinetic actions. Regulatory authorities encourage the pharmaceutical industry to develop single isomers of chiral drugs. Thus, methods are required which are suitable for stereospecifically evaluating the enantiomers of a drug in quality control of enantiomerically pure drugs, e.g. the determination of the enantiomeric excess (ee). Beside the major methods, chiral HPLC and NMR spectroscopy, cyclodextrin-modified capillary electrophoresis is enjoying increasing popularity in both academic and industrial laboratories. In order to obtain a baseline separation of mixture of a minor and a major isomer which is appropriate for determining the ee, the following parameters have to be optimised: the nature and concentration of the cyclodextrin derivative, the composition of the background electrolyte, the pH value, the organic modifier, and the kind and conditioning of the capillary. In addition, the sensitivity of detection has to be taken into consideration, because a limit of detection of 0.1 percent is necessary to fulfil the requirements of the ICH guidelines. Strategies of method development will be discussed using currently reported examples.