Application of sulfobutylether-beta-cyclodextrin with specific degrees of substitution for the enantioseparation of pharmaceutical mixtures by capillary electrophoresis

In this research the separation of the enantiomers of the basic drug bidiso mide (SC-40230) from five closely related known process impurities was inve stigated using several neutral and anionic sulfobutylether beta-cyclodextri ns (SBE-beta-CDs) as isomer selectors. Several novel sulfobutylether deriva tive mixtures and purified charge types having a specific degree of substit ution were used to study the effect of selector charge on the efficiency an d selectivity of both chiral and achiral separations. The effects of run bu ffer pH, selector type, and selector concentration on the chiral separation of bidisomide and the achiral separation of the related process impurities was also investigated. The related process impurity, SC-47500, displayed s ignificant peak tailing with SBE-beta-CD mixtures which contained mono- to deca-substituted cyclodextrins. This problem was explored using isolated SB E-beta-CD charge types having degrees of substitution from one to seven. Pe ak tailing increased as the charge on the selector increased, suggesting th at the distortion was due to electrodispersion and the large countercurrent mobility of the negatively charged complexes. Pure charge types having a l ower degree of substitution provided adequate chiral and achiral selectivit y, while eliminating the severe peak distortion caused by electrodispersion . The complete analysis of the bidisomide enantiomers and the related impur ities was achieved with a pH 2.5 running buffer containing 5-10 mM of the i solated sulfobutylether charge types SBE[2](ds)(1)(sr)-beta-CD or SBE[3](ds )(1)(sr)-beta-CD. These conditions gave baseline resolution of bidisomide e nantiomers and all five impurities, thus allowing both chiral and achiral p urity to be determined in a single run.