Comparison of sulfobutylether- and sulfated-beta-cyclodextrins as additives for the chiral separation of basic spirobenzopyrans by capillary electrophoresis

Three charged substituted beta-cyclodextrins (beta-CDs), sulfobutylether-be ta-(SBE-beta-CD), degree of substitution (DS) 4 and 7), and sulfated-beta-( S-beta-CD) cyclodextrins, were compared as chiral additives in capillary el ectrophoresis for the enantiomeric separation of basic spirobenzopyran deri vatives (pK(a) 9.9) which differ from each other by an N-alkyl group. The n umber of sulfobutylether groups attached to the cyclodextrin moiety signifi cantly influences the enantioseparation of the basic drugs. SBE-beta-CD (DS 7) which is more strongly bound to cationic analyte than SBE-beta-CD (DS 4 .6), requires smaller concentrations to achieve the same resolution. Beside s, better enantioresolutions were obtained with S-beta-CD rather than with SBE-beta-CDs though higher concentrations are required, which led to high c urrent values. However, both pairs of enantiomers cannot be resolved using S-beta-CD while SBE-beta-CDs make it possible to resolve simultaneous enant ioseparation of such solutes slightly differing in hydrophobicity. This sup ports the hypothesis that hydrophobic interactions (outside of the CD cavit y) between the butyl group attached to SBE-beta-CD and the N-alkyl group of spirobenzopyran play a role in the enantioseparation. On the other hand, t he sulfate group of S-beta-CD was directly attached to the CD moiety which means that the S-beta-CD-drug complexation mechanism arises through the com bination of electrostatic and hydrophobic (inside the CD cavity) interactio ns. Finally, enantiomers of spirobenzopyran drugs were satisfactorily resol ved by CE using a 20 mg/mL S-beta-CD concentration (resolution 4.0), 7 mg/m L SBE-beta-CD DS 4 (resolution 1.3), or 5 mg/mL SBE-beta-CD DS 7 (resolutio n 3.3) added to the phosphate buffer (pH 2.6, 50 mM ionic strength).