Preparative enantioseparation of β-blocker drugs by counter-current chromatography using dialkyl l-tartrate as chiral selector based on borate coordination complex

Counter-current chromatography (CCC) was applied for preparative enantioseparation of three β-blocker drugs, including propranolol, pindolol and alprenolol. The two-phase solvent system was composed of chloroform–0.05 mol L−1 acetate buffer containing 0.10 mol L−1 boric acid (1:1, v/v), in which 0.10 mol L−1 di-n-hexyl l-tartrate was added in the organic phase as chiral selector. Influence factors in the enantioseparation of propranolol were investigated. The chromatographic retention mechanism based on borate coordination complex was proposed. 116 mg of racemic propranolol was completely enantioseparated using conventional high speed CCC in a single run, yielding 48 mg of (+)-propranolol with HPLC purity of 98.9% and 47 mg of (−)-propranolol with HPLC purity of 96.3%. Recovery for propranolol enantiomers from CCC fractions was in the range of 75–82%. pH-zone-refining CCC was also successfully applied in enantioseparation of propanolol and it was found that 356 mg of racemic propranolol could be completely enantioseparated. 145 mg of (+)-enantiomer with HPLC purity of 95.6% and 148 mg of (−)-enantiomer with HPLC purity of 98.2% were recovered from pH-zone-refining mode. Separation mechanism about chiral separation by pH-zone-refining CCC was discussed.

► High speed counter-current chromatography was applied in enantioseparation of three β-blocker drugs.
► The two-phase solvent system with chiral selector for enantioseparation was selected and optimized.
► The chromatographic retention mechanism for enantioseparation was proposed.
► pH-zone-refining counter-current chromatography was successfully applied in enantioseparation of propanolol.
► Separation mechanism about chiral separation by pH-zone-refining CCC was discussed.