Enantiomeric separation of chiral drugs by using capillary electrophoresis chromatography with chiral selectors.

摘要

Purpose. Natural vitamin E has been reported to be twice as potent as synthetic vitamin as an antioxidant. Therefore, we report the development of enantiomeric separations for dl-alpha-tocopherol by micellar electrokinetic chromatography using (+)-bile acids as chiral selectors and dl-alpha-tocopheryl succinate using vancomycin as chiral selector. Capillary electrophoresis using cyclodextrin derivatives has been known as effective way for enantiomeric separations. In this research study, chiral separation of chiral drugs is developed by CE with single isomer hepatakis-6-sulfato-beta-cyclodextrin and single isomer heptakis-(2,3-diacetyl-6-sulfato)-beta-cyclodextrin.; Methods. dl-alpha-Tocopherol was separated by micellar electrokinetic chromatography using 7 mM borate and 14 mM phosphate mixed buffer pH 9.2 containing 50 mM SDS, 30 mM (+)-bile acid and 15% acetonitrile. dl-alpha-Tocopheryl succinate was separated using 0.1 M phosphate buffer pH 7 with 5 mM vancomycin. Chiral drugs were separated with 50 mM phosphate buffer at both acidic and basic pH including HS-beta-CD and HDAS-beta-CD as chiral selector.; Results. The best resolution (Rs = 1.53) of 2R and 2S of alpha-tocopherol was achieved with SDS, taurodeoxycholate and acetonitrile. Resolution of 2R and 2S of alpha-tocopheryl succinate was achieved with vancomycin. However, vancomycin could not separate dl-beta-tocopheryl succinate. Enantiomeric separations were obtained for (+/-)-fenfluramine, (+/-)-isoproterenol and (+/-)-propranolol in pH 2.5 with 10--15 mM HS-beta-CD concentrations. However, enantiomers of atropine were separated with high resolution at pH 10 using HS-beta-CD as chiral selector. The effect of pH on the enantiomeric separation using HDAS-beta-CD was completely opposite in separation than with HS-beta-CD. Also, enantiomeric separation using HS-beta-CD showed better resolution than separation with HDAS-beta-CD.; Conclusion. The 2R and 2S enantiomers of alpha-tocopherol were separated with MEKC using (+)-bile acids as chiral selectors. Hydrogen bonding between the phenolic OH group and 1-O ether of alpha-tocopherol and the 12alpha-hydroxy and the amide group of the taurocholate may be contributing factors in their resolution. The 2R and 2S enantiomers of dl-alpha-tocopheryl succinate were separated using vancomycin as chiral selectors. (+/-)-Fenfluramine, (+/-)-isoproterenol, (+/-)-atropine and (+/-)-propranolol were separated with good resolution using HS-beta-CD and HDAS-beta-CD as chiral selector showing interaction between analyte and chiral selector.