Enantioseparation of beta-blockers with two chiral centers by capillary electrophoresis using sulfated beta-cyclodextrins.

Abstract

Capillary electrophoresis methods for the enantioresolution of two beta-blockers possessing two chiral centers--labetalol and nadolol--were developed using electrokinetic chromatography. These methods were based on the addition of sulfated beta-cyclodextrins (S-betaCD) as chiral selectors to the background electrolyte (BGE). Different operating parameters (pH and ionic strength of the BGE, concentration of S-beta-CD) were investigated using a normal or reversed polarity mode. A complete resolution of the four isomers of labetalol was obtained either at the cathode or at the anode according to the pH of the BGE. The resolution of nadolol was observed whatever polarity of the applied voltage but a baseline separation of the four enantiomers within a time of analysis appropriate to routine assay was only obtained at the anode. This optimal separation was performed using high concentrations of chiral additive in an acidic pH buffer of low molarity. Besides the complete enantiomeric separation of the beta-blockers studied, the interest of the proposed methods is to permit a reversal of the migration order of the different enantiomers. This could be of high interest in quality control for the study of enantiomeric purity, which is now required for the development of drugs and chemicals.