正交试验优选拆分5种碱性药物的毛细管电泳法

目的以羧甲基-β-环糊精(carboxymethyl-β-cyclodextrin,CM-β-CD)为手性选择剂,用毛细管电泳法(capillary electrophoresis,CE)对5种碱性药物苯磺酸氨氯地平(amlodipine besilate)、二氧丙嗪(dioxopromethazine)、硫酸特布他林(terbutaline sulfate)、氢溴酸后马托品(homatropinehydrobromide)和盐酸美普他酚(meptazinol hydrochloride)进行对映体分离研究。方法采用正交试验设计的方法考察3个水平数背景电解质溶液的pH值、CM-β-CD浓度、缓冲盐浓度对对映体分离的影响,优化了分离条件。结果在最优分离条件下,苯磺酸氨氯地平、二氧丙嗪、硫酸特布他林、氢溴酸后马托品、盐酸美普他酚对映体达到良好分离,分离度分别为12.6、4.4、6.0、5.7、3.5。结论 CM-β-CD对5种碱性药物均具有较好的对映体选择性。

Enantioseparation of five basic drugs by orthogonal experimental design method

Objective To establish a capillary electrophoresis(CE) method for separating amlodipine besilate, dioxopromethazine, terbutaline sulfate, homatropine hydrobromide and meptazinol hydrochloride. Methods Carboxymethyl-β-cyclodextrin (CM-β-CD) was used as a chiral selector. The basic chemical parameters of enantioseparation, such as chiral selector concentration, buffer concentration and buffer pH, were optimized using an orthogonal experimental design. Results Under the optimized conditions, amlodipine besilate, dioxopromethazine, terbutaline sulfate,homatropine hydrobromide and meptazinol hydrochloride were separated with the maximum resolution factors of 12.6, 4.4, 6.0, 5.7 and 3.5, respectively. The migration order of (S)-(-)- and (R)-(+)- amlodipine besilate was determined by spiking the sample with non-racemic analyte. Conclusions CM-β-CD has a good enantioselectivity on the five kinds of drugs; orthogonal experimental design is a convenient , effective method for chiral separation．