高效毛细管电泳法分离氟西汀和联苯苄唑的对映体

Separation of Fluoxetine and Bifonazole Enantiomer by High Performance Capillary Electrophoresis

目的:建立拆分氟西汀和联苯苄唑两种药物手性对映体的方法。方法:采用高效毛细管电泳法,以羧甲基-β-环糊精(CM-β-CD)为手性选择剂,以未涂层熔融石英毛细管柱为分析柱,重力进样5 s,高度差10 cm,柱温20℃。分别对缓冲盐浓度、手性选择剂的浓度、缓冲盐的pH、分离电压进行考察,确定两种药物最佳分离条件;并以分离度为指标对两种药物的原料药进行分离验证试验。结果:氟西汀对映体在pH 4.5的30 mmol/LNaH2PO4缓冲溶液(含1.0%CM-β-CD)为运行电解质时达到最佳分离,分离度为3.70;联苯苄唑对映体在pH 3.0的30 mmol/LNaH2PO4缓冲溶液(含1.0%CM-β-CD)为运行电解质时达到最佳分离,分离度为5.44。方法精密度的RSD均≤0.9%(n=6)。结论:CM-β-CD的加入对氟西汀和联苯苄唑有很高的对映体选择性,可有效分离两种药物;建立的方法精密度好、经济、简便、快捷。

OBJECTIVE ： To establish the method for the separation of chiral enantiomers of fluoxetine and bifonazole. METHODS： High performance capillary electrophoresis was established using carboxymethyl-β-cyclodextrin （CM-β-CD） as chiral selective agent; the separation of enantiomers was performed on uncoated fused-silica capillary column with gravity sampling time of 5 s, height difference of 10 cm and column temperature of 20 ℃; the concentration and pH value of phosphate buffer, the concentration of chiral selective agent and the separation voltage were investigated, and the optimal separation condition of 2 kinds of drugs were determined. The validation test of 2 kinds of raw materials was conducted using separation rate as index. RESULTS： Under the optimal conditions, the resolutions of fluoxetine and bifonazole enantiomers were 3.70 and 5.44 by using 30 mmol/L NaH3PO4 buffer solution （pH 4.5 and 3.0, containing 1.0% CM-β-CD） as running electrolyte, respectively. RSD of method precision was 0.9% （n=6）. CONCLUSIONS： CM-β-CD is high enantio-selective for the fluoxetine and bifonazole and can separate them effectively. The method is accurate, economical, convenient and rapid.