Enantioseparation of pheniramine enantiomers by high-speed countercurrent chromatography using β-cyclodextrin derivatives as a chiral selector.

Abstract

The enantioselective separation of pheniramine was studied by a high-speed countercurrent chromatography method using β-cyclodextrin derivatives as a chiral selector. Several key variables, for instance, type of organic solvent and chiral selector, concentration of chiral selector, pH value of aqueous phase, and temperature on the enantioselectivity, were investigated systematically by liquid-liquid extraction experiments. Combining the results of extraction experiments and high-speed countercurrent chromatography, the most suitable conditions for separation of pheniramine enantiomers were obtained with the two-phase system that consisted of isobutyl acetate/aqueous phase, containing 0.02mol/L carboxymethyl-β-cyclodextrin, pH8.50 at 278.15K. Under the optimal conditions, pheniramine enantiomer was successfully resolved after four cycles of high-speed countercurrent chromatography. By using high-performance liquid chromatography to analyze the fractions, the purities of both (+)-pheniramine and (-)-pheniramine were over 99% and the recoveryofthismethodwasupto 85-90%.