Electrophoretic separation strategy for chiral pharmaceuticals using highly-sulfated and neutral cyclodextrins based dual selector systems

The enantiomeric separation of chiral pharmaceuticals was investigated using dual systems with mixtures of cyclodextrin derivatives. The dual cyclodextrin systems, consisting of one highly-sulfated (alpha-, beta-, and gamma-HSCD) and one neutral cyclodextrin, i.e. either heptakis (2,3,6-tri-O-methyl)-beta-CD (TMCD), heptakis (2,6-di-O-methyl)-beta-CD (DMCD) or hydroxypropyl-beta-CD (HPCD), are tested on 25 pharmaceutical compounds with different acid-basic properties (16 basics, 8 acids and I neutral). The influence on the separation of the type and concentration of neutral CD in highly-sulfated cyclodextrins-based dual selector systems, is investigated. For 11 of 16 basic compounds, a better separation is obtained with the CD mixtures compared to the use of only a highly-sulfated CD. Mixtures with TMCD give better results than those with DMCD and HPCD. Results showed that dual CD systems are useful to achieve and to optimise chiral separations of compounds not (sufficiently) separated with HSCDs alone. For example, ibuprofen was not resolved with alpha-, beta- or gamma-HSCD, but could be separated with the mixture 25 mM TMCD and 5% HS-beta-CD. Based on the obtained results, a dual CD systems based separation strategy is defined. (C) 2004 Elsevier B.V. All rights reserved.