新型混合取代环糊精毛细管电泳对药物的手性分离..doc

新型混合取代环糊精毛细管电泳对药物的手性分离 应津津1，梅洁1，肖玉秀1*，任勇2（1.武汉大学药学院，武汉430072；2.南京师范大学药物超分子材料及应用实验室，南京210046）药物超分子材料及应用实验室:目的　考察新型混合取代环糊精衍生物羟丙基-磺丁基-?-环糊精(HP-SBE- ?-CD) 对四种碱性药物的对映体分离，并比较其与单一取代环糊精衍生物手性识别能力的强弱。方法　采用毛细管区带电泳模式，研究HP-SBE-?-CD对手性药物的拆分，探讨环糊精浓度和取代度、缓冲液的pH值和浓度、有机改性剂含量以及分离电压对碱性药物对映体手性分离的影响；比较HP-SBE-?-CD、羟丙基-?-环糊精 (HP-?-CD) 与磺丁基-β-环糊精 (SBE-?-CD) 手性拆分能力的强弱。结果　电泳条件为Tris-磷酸盐缓冲液(pH 2.5, 60 mmol·L– 1)，运行电压18 kV，有机改性剂甲醇含量15%时，四种碱性药物达到较好分离；手性识别能力大小SBE-?-CD HP-SBE-?-CD HP-?-CD。结论　本实验对HP-SBE-?-CD手性拆分的初步探究可为混合取代环糊精衍生物的应用和具有高手性分离能力的衍生化环糊精的合成提供重要依据。 关键词: 手性分离；羟丙基-磺丁基醚-?-环糊精；毛细管电泳；结合常数 Chiral separation of drugs by capillary electrophoresis with a new mixed-substituted cyclodextrin ABSTRACT: OBJECTIVE To investigate the enantioseparation of four basic drugs using capillary electrophoresis (CE) with a new mixed-substituted derivative of cyclodextrin，hydroxypropyl-sulfobutylether-?-cyclodextrin (HP-SBE-?-CD), and compare the chiral recognition ability of HP-SBE-?-CD with that of mono-substituted derivatives. METHODS The effects of concentration and substitution degree (SD) of HP-SBE-?-CD, concentration and pH value of electrophoretic buffer, the organic modifier, separation voltage on enantioseparation of basic drugs were investigated; also, the chiral separation abilities of HP-SBE-?-CD, hydroxypropyl-?-cyclodextrin (HP-?-CD) and sulfobutylether-?-cyclodextrin (SBE-?-CD) were compared. RESULTS Good separation was achieved under the following conditions: running buffer, 60 mmol·L– 1 Tris-phosphate buffer(pH 2.5); running voltage , 18 kV ; organic modifier, 15% methanol (v/v). The ability of chiral separation: SBE-?-CD HP-SBE-?-CD HP-?-CD. CONCLUSION　The initial investigation on the new HP-SBE-?-CD was carried out, providing import basis for the application of mixed-substituted CD derivatives and the synthesis of new CD derivatives with high chiral recognition ability. KEY WORDS: chiral separation; hydroxypropyl-sulfobutylether-?-cyclodextrin; capillary electrophoresis; binding cons