Comparative capillary electrophoresis and NMR studies of enantioseparation of dimethindene with cyclodextrins

Enantioseparation of the antihistaminic drug dimethindene (DIM) (as maleate and tartrate salts) was studied using various cyclodextrins (CD) as chiral selectors in capillary electrophoresis (CE). NMR spectroscopy was used in order to elucidate the reason for the opposite migration order of the enantiomers of dimethindene (DIM) when native beta-CD or commercially available carboxymethyl-beta-CD (CM-beta-CD) were used. This study demonstrated that the complexation-induced chemical shift of enantiomers does not always definitely show the chiral recognition pattern. The binding constants between the analyte and chiral selector need to be determined. NMR spectroscopy provided clear evidence on the multimodal (at least bimodal) complexation between DIM and CM-beta-CD. These complexes seem to have a different stoichiometry. Moreover, the chiral recognition of DIM seems to be opposite in these complexes. The effect of additives such as urea on the interaction between DIM and beta-CD was studied with both techniques. (C) 1998 Elsevier Science B.V.