毛细管区带电泳同时分离维拉帕米和去甲维拉帕米对映体

 目的：建立同时分离维拉帕米(VPM)和去甲维拉帕米(NVPM)对映体的高效毛细管电泳方法。方法：采用目前应用最广泛的毛细管区带电泳模式，以三甲基-β-环糊精(TM-β-CD)为手性选择剂，考察了毛细管柱、进样方式、运行电压、缓冲液pH值、溶剂等因素对峰迁移、分辨率、灵敏度的影响，选择优化的电泳条件用于标准溶液的分离和测定。结果：用pH为2.5，含60mmol·L^-1TM-β-CD的60mmol·L^-1磷酸盐缓冲液为手性拆分剂，在75μm(ID)×30cm的聚内酰胺涂渍柱（柱温20℃）上，采用12kV(7s)电迁移进样，运行电压为154kV，紫外检测波长200nm，能在11min内将内标(Gallopamil)、R-VPM、S-VPM、R-NVPM和S-NVPM完全分离，并用各对映体与内标的峰面积比为定量指标进行水标溶液的浓度测定，定量检测限为25ng·ml^-1，日间变异小于10%，线性关系良好。结论：毛细管区带电泳方法能快速、高效地分离VPM和NVPM对映体，为VPM和NVPM对映体的测定及质量控制提供新的方法，为生物体液中VPM及其代谢物NVPM对映体的测定，为开展VPM对映体特异性的药动学和药效学研究打下基。

Simultaneous chiral separation of verapamil and norverapamil by capillary zone electrophoresis

OBJECTIVE: To separate simultaneously the verapamil (VPM) and norverapamil (NVPM) enantiomers in standard solutions by capillary zone electrophoresis. METHOD: TM-β-CD was selected as chiral selector. Many factors that can affect the enantiomeric resolution, including capillary type, injection mode, injection voltage, running voltage, the pH value of buffer and types of sample solvent were investigated to optimize the experiment condition. The standard solutions of each enantiomer were determined under the optimum electrophoresis conditions. RESULTS: Good separation was achieved under the following conditions: capillary, 75 μm (ID)×30 cm, coated; setpoint, 20 ℃; detector, UV 200 nm; injection, 12 kV, 7 s; running voltage, 14 kV; running buffer, 60 mmol·L^-1TM-β-CD 60 mmol·L^-1 phosphate buffer, pH 2.5; sample solvent, doubly distilled water. The migration times were less than 11 min. The inter-day relative standard deviation of standard solutions were less than 10%. The limit of quantification was 25 ng·ml^-1. CONCLUSIONS: The enantiomers of VPM and NVPM can be separated quickly with TM-β-CD by capillary zone electrophoresis. This novel method could be used for the simultaneous determination of the plasm concentrations of VPM and NVPM enatiomers in the study of pharmacokinetics and pharmacodynamics.