10种手性药物对映体毛细管电泳拆分方法及机理探讨

Enantioseparation of Drugs by Capillary Electrophoresis and Their Separation Mechanism

本文采用毛细管区带电泳方法,在50 mmol.L-1磷酸盐-三乙胺缓冲体系中(pH 2.5),以高磺化-β-环糊精为手性选择试剂,在40 min内同时基线分离了扑尔敏、盐酸异丙肾上腺素等10种药物的手性对映体。研究了缓冲溶液组成、手性选择剂类型、分离电压和温度等因素对分离效果的影响。对手性拆分机理进行了初步探讨,发现高磺化环糊精对含氨基的碱性取代芳烃类药物的分离效果最好,而且与氨基的存在形式有较大的关系,若分离对象中含有叔胺将对手性拆分起着决定性作用。

Using capillary zone electrophroesis method, ten pharmaceuticals including Chlorpheniramine and Isoprenaline were simultaneous baseline enantioseparated in 40 min in phosphate-triethylamine buffer solution （pH=2.5, 50 mmol·L^-1） with 5% highly sulfated β-cyclodextrin as chiral additive. The effects of the composition of buffer, chiral selector, running voltage and temperature on the enantioseparation were investigated. The separation mechanism was also studied and the results revealed that the highly sulfated cyclodextrin was an especially efficient resolution reagent for enantioseparation of arenes drugs containing amine substituents. The resolution was highly dependent on the forms of amine substituents and the tertiary amine substituent existing in the drug enantiomers.