Enantiomer separation of drugs by capillary electrophoresis using mixtures of beta-cyclodextrin sulfate and neutral cyclodextrins.

Abstract

Direct separation of enantiomers of drugs was investigated by capillary electrophoresis employing mixtures of charged cyclodextrin derivatives (CDs) and electrically neutral CDs (i.e., dual CD system). Among various charged CDs employed, it was found that beta-CD sulfate showed relatively wide enantioselectivity for a wide variety of drugs under acidic conditions. Then separation of enantiomers was performed by employing beta-CD sulfate and the effect of the addition of electrically neutral CDs to the buffers containing beta-CD sulfate was investigated. Through the addition of electrically neutral CDs to the buffers containing the charged CD, resolution of most of the enantiomers was improved, compared with those with the charged CD alone. It was also found that the ring size (alpha, beta, gamma,), the substitution groups and the concentration of the additional electrically neutral CDs affected the enantioselectivity. For example, alpha-CD addition was effective for the separation of enantiomers of chlorpheniramine and hydroxypropyl-beta-CD was effective for the enantiomer separation of trimetoquinol isomer. The application of the method in optical purity testing is also briefly mentioned.