Separation of atropisomers of anti-hepatitis drug dimethyl diphenyl bicarboxylate analogues by capillary electrophoresis with vancomycin as the chiral selector

Abstract

Separation of atropisomers of analogues of the anti-hepatitis drug dimethyl diphenyl bicarboxylate (DDB) by capillary electrophoresis with vancomycin as the chiral selector is described. Among several tested chiral selectors, including various cyclodextrin derivatives as well as vancomycin, only the latter displayed the enantioselectivity to the studied atropisomers. However, relatively poor separation efficiency was obtained due to the adsorption of vancomycin on the capillary wall. This problem was overcome by modifying the capillary wall with a polycationic electrolyte named hexadimethrine bromide (HDB) to produce a positively charged coating, which minimized the adsorption of vancomycin on the capillary wall by electrostatic repulsion. Moreover, the positively charged coating could shorten the separation time by reversing the EOF because the reversed EOF migrated to the same direction as the negatively charged analyte. Effects of buffer pH, vancomycin and buffer concentrations and applied voltage on the separation were investigated and the optimal conditions were established as follows: 40 mM Tris–phosphate buffer (pH 6.0) containing 6.0 mM vancomycin and 0.001% HDB. Baseline separation of three racemic DDB analogues was obtained within 12 min under the optimal conditions.