氯维地平原料药中有机溶剂残留量测定

Determination of residual organic solvents in raw material clevidipine

目的：建立氯维地平原料药中有机溶剂残留量测定的方法。方法：采用顶空气相色谱法测定氯维地平原料药中乙醇、丙酮、异丙醇、乙腈、二氯甲烷、异丙醚和乙酸乙酯的残留量。结果：乙醇、丙酮、异丙醇、乙腈、二氯甲烷、异丙醚和乙酸乙酯的定量限分别为15.93、2.01、15.16、5.45、7.85、1.87和0.47μg/ml,检测限分别为3.98、0.50、3.79、2.73、3.93、0.47和0.14μg/ml,线性范围分别为63.71～1 019.4μg/ml（r=0.999 8）,64.25～1028μg/ml（r=0.999 9）,60.63～970μg/ml（r=0.999 8）,5.45～87.2μg/ml（r=0.999 9）,7.85～125.6μg/ml（r=0.999 9）,59.86～957.8μg/ml（r=0.999 2）,61.28～980.4μg/ml（r=0.999 9）。平均加样回收率为96.2%～104.5%,精密度RSD为2.2%～3.7%。结论：该方法准确可靠,重现性好,可用于氯维地平原料药中有机溶剂残留量的控制。

Objective：To establish a method for the determination of residual organic solvents in raw material clevidipine（RMC）.Methods：Residual ethanol,acetone,isopropanol,acetonitrile,dichloromethane,isopropyl ether and ethyl acetate ether in RMC were determined by headspace gas chromatography.Results：The quantitative limits were 15.93,2.01,15.16,5.45,7.85,1.87 and 0.47μg/ml,and the detection limits were 3.98,0.50,3.79,2.73,3.93,0.47 and 0.14μg/ml for ethanol,acetone,isopropanol,acetonitrile,dichloromethane,isopropyl ether and ethyl acetate,respectively.Linearity was achieved within the ranges of 63.71-1 019.4μg/ml（r=0.999 8）for ethanol,64.25-1028μg/ml（r=0.999 9）for acetone,60.63-970μg/ml（r=0.999 8）for isopropanol,5.45-87.2μg/ml（r=0.999 9）for acetonitrile,7.85-125.6μg/ml（r=0.999 9）for dichloromethane,59.86-957.8μg/ml（r=0.999 2）for isopropyl ether and 61.28-980.4μg/ml（r=0.999 9）for ethyl acetate,respectively.The average recovery rates were 96.2%-104.5% and the precision RSD was 2.2%-3.7%.Conclusion：The method was accurate,reliable and reproducible,and could be used for the determination of the above residual organic solvents in RMC.