Enantiomeric separation of ( R, S)-naproxen by recycling high speed counter-current chromatography with hydroxypropyl-β-cyclodextrin as chiral selector

Abstract

Recycling high speed counter-current chromatography (HSCCC) was successfully applied to resolution of ( R, S)-naproxen (NAP) using hydroxypropyl-β-cyclodextrin (HP-β-CD) as chiral selector. The two-phase solvent system composed of n-hexane–ethyl acetate–0.1 mol L −1 phosphate buffer solution with pH = 2.67 (8:2:10, v/v/v) was selected. Influence factors for the chiral separation process were investigated, including concentration of HP-β-CD, equilibrium temperature and pH of aqueous phase. Suitable elution mode was selected for HSCCC enantioseparation of ( R, S)-NAP. Under optimum separation conditions, 29 mg of ( R, S)-NAP was separated using preparative recycling HSCCC with the molar ratio HP-β-CD/NAP racemate 83:1. Technical details for recycling elution mode were discussed as for chiral HSCCC separation. The purities of both ( S)-NAP and ( R)-NAP were over 99.5% as determined by HPLC. Enantiomeric excess of ( S)-NAP and ( R)-NAP reached 99.4%. Recovery for NAP enantiomers from HSCCC fractions was 82–89%, yielding 13 mg of ( S)-NAP and 12 mg of ( R)-NAP.