Separation of basic drug enantiomers by capillary electrophoresis using methylated glucuronyl glucosyl β-cyclodextrin as a chiral selector

Abstract

Separations of basic drug enantiomers by capillary electrophoresis have been investigated using methylated glucuronyl glucosyl β-cyclodextrin (Me GUG β-CD) as the chiral selector in the background electrolyte. Methylation was performed by reaction with methyl iodide, barium oxide, and barium hydroxide in dimethylformamide, varying the reaction temperature and time. The resulting Me GUG β-CD derivatives differed in their degree of substitution and were characterized using matrix-assisted laser desorption ionization time-of-flight mass spectra. Among the Me GUG β-CD derivatives prepared, the one with a degree of substitution of 2.8 showed the highest resolution abilities for basic drug enantiomers. Chiral resolution of 16 basic drugs was attained using the Me GUG β-CD derivative (10 mM solution in 40 mM sodium phosphate buffer at pH 3.5). The chiral recognition abilities of Me GUG β-CD were compared with those of GUG β-CD. Me GUG β-CD showed higher resolution for bupivacaine, clorprenaline, isoprenaline, pindolol, salbutamol, and terbutaline than GUG β-CD, while GUG β-CD showed higher resolution for atenolol, chlorpheniramine, dimethindene, homochlorcyclizine, ketamine, piperoxan, promethazine, propranolol, trimetoquinol, and verapamil than Me GUG β-CD. Thus, Me GUG β-CD and GUG β-CD can be complementarily used for the resolution of basic drug enantiomers.