顶空气相色谱法测定尼伐地平中的残留溶剂

Determination of residual solvents in nivaldipine by headspace gas chromatography

目的建立顶空气相色谱法测定尼伐地平原料药中5种残留有机溶剂的方法。方法色谱柱为DB-624(30 m×0.53 mm,3μm),氢火焰离子化检测器(FID),进样口温度为200℃,检测器温度为250℃,顶空平衡温度为80℃,顶空平衡时间为30 min,程序升温40℃保持8 min,以10℃min-1的速度升至180℃并保持5 min,N,N-二甲基甲酰胺(DMF)为溶剂。结果 5种有机溶剂和DMF的峰完全分离,且线性关系良好,平均回收率为乙醇102.1%、丙酮99.4%、异丙醇97.9%、乙酸乙酯98.9%和甲苯100.2%。5种残留溶剂的检出量均符合2010版中国药典规定(乙醇、丙酮、异丙醇和乙酸乙酯限度均为0.5%,甲苯为0.089%)。结论该方法操作简单,结果可靠,可用于尼伐地平原料药中的残留有机溶剂的测定。

Objective To establish a headspace gas chromatography method for the determination of residual solvents in nivaldipine.Methods DB-624 capillary column（30 m×0.53 mm,3 μm） and hydrogen flame ionization detector were used.The injector temperature was 200 ℃.The detector temperature 250 ℃.The oven temperature started at 40 ℃.After 8 min,the temperature was programmatically increased to 180 ℃ at 10 ℃ min-1.The N,N-dimethylformamide was used as solvent.Results The 5 residual solvents（ethanol,acetone,isopropyl alcohol,acetic ether,and methyl benzene） and solvent DMF were separated completely and presented a good linear relationship.The average recovery was 102.1%（ethanol）,99.4%（acetone）,97.9%（isopropyl alcohol）,98.9%（acetic ether） and 100.2%（methyl benzene）.The residue of the 5 organic solvents was in accordance with Chinese Pharmacopoeia.The limit of ethanol,acetone,isopropyl alcohol and acetic ether was 0.5%,and that of methyl benzene was 0.089%.Conclusion The method is practical,reproducible and reliable.It can be used for the determination of the residual organic solvents in nivaldipine.