西布曲明对映体的毛细管电泳分离与定量分析方法研究

Chiral Separation and Quantitative Analysis of Sibutramine by Capillary Electrophoresis

目的:采用毛细管电泳分离西布曲明手性异构体,建立准确、快速的定量分析西布曲明及其对映体的方法。方法:对运行缓冲液离子强度、pH、手性选择剂浓度、有机溶剂添加剂、毛细管内径进行了选择。电泳条件为:石英毛细管柱内径75μm,总长65.0 cm,有效长度51.6 cm;紫外检测波长223nm;分离电压18 kV;温度25℃;电动力进样,进样电压18 kV,进样时间3s。结果:在20 mmol·L-1β-环糊精、30 mmol·L-1磷酸盐、pH 5.40的运行缓冲液中,西布曲明对映体达到了基线分离。西布曲明在0.031-0.412 mg·mL-1浓度范围内,线性关系良好,两对映体的检测限分别为11 μg·mL-1和10 μg·mL-1。在制剂其它成分共存时西布曲明的回收率为96.9%,2种对映体的回收率分别为95.1%及98.7%。结论:在该条件下可以成功分离西布曲明对映体,并建立起西布曲明对映体定量分析的毛细管电泳方法。

Objectives: The enantiomeric separation of sibutramine by capillary electrophoresis using β-cyclodex trin as the chiral selector was studied. In order to determine sibutramine and its enantiomers,a quantitative method was set up. Methods: The effect of pH and concentration of electrophoretic running buffer, the concentration of β CD,organic additive and the internal diameter of the capillary on enantioseparation were investigated respectively. The separation was performed at 25℃ on a fused - silica capillary of 75 μm×65.0 cm, effective length 51.6 cm. The applied high voltage was 18 kV from anode to cathode and the detection wavelength was 223 nm. Samples were injected into the capillary by electrokinetic force at 18 kV for 3 seconds. Results:In the running buffer composed of 30 mmol·L-1 phosphate containing 20 mmol·L-1β- cyclodextrin, at pH 5. 40, the two enantiomers could be well separated. The linear concentration region of sibutramine was 0. 031-0. 412 mg·mL-1. The lowest detective concentration of two enantiomers were 11μg·mL-1 and 10 μg ?*** mL-1. The recoveries of sibutramine and two enantiomers with other constitutents in capsules were 96. 9% ,95. 1% and 98. 7% ,respectively. Conclusions: Under the optimal operation condition, the enantiomers of sibutramine were separated at baseline in the electropherogram. The quantitative analytical method of sibutramine and its enantiomers was set up.