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目的:建立以羧甲基-β-环糊精(CM-β-CD)为手性选择剂的毛细管电泳法检查R-维拉帕米原料药中S-异构体杂质。方法:实验考察了CM-β-CD质量浓度、p H及缓冲溶液浓度对对映体分离的影响。优化后的毛细管电泳条件为毛细管柱为未涂壁熔融石英毛细管柱,背景电解质为30 mmol·L~(-1)磷酸盐缓冲液,pH 4.0,手性选择剂为质量浓度为15 g·L~(-1)的CM-S-β-CD。结果:在上述毛细管电泳条件下,维拉帕米S-异构体与R-异构体能够实现良好分离,分离度>5.0。维拉帕米S-异构体在质量浓度为2.0~20μg·m L~(-1)范围内呈现良好的线性关系(r>0.999),加样回收率为95.5%~103.5%,该方法的精密度和重复性均良好。3批R-维拉帕米原料药经本法检测所含S-异构体杂质均小于0.2%。结论:所建立好的方法适于R-维拉帕米原料药中S-异构体杂质的检查。
OBJECTIVE: To establish a method for the determination of S-isomer impurities in R-verapamil by capillary electrophoresis with carboxymethyl-β-cyclodextrin (CM-β-CD) as chiral selector. Methods: The effects of CM-β-CD concentration, p H and buffer concentration on the enantiomeric separation were investigated experimentally. The optimized capillary electrophoresis conditions were as follows: the capillary column was an uncoated fused silica capillary column, the background electrolyte was 30 mmol·L -1 phosphate buffer, pH 4.0 and the concentration of chiral selector was 15 g · L ~ (-1) CM-S-β-CD. Results: Under the above capillary electrophoresis conditions, the S-isomer of verapamil and the R-isomer can be well separated with a resolution> 5.0. Verapamil S-isomer showed good linearity (r> 0.999) in the range of 2.0 ~ 20μg · m L -1 with the recoveries of 95.5% ~ 103.5% The precision and repeatability are good. Three batches of R-verapamil raw materials tested by this Act contain S-isomer impurities are less than 0.2%. Conclusion: The established method is suitable for the examination of S-isomer impurity in R-verapamil.