离子液体-顶空气相色谱法同时检测甲苯磺酸索拉非尼原料中6种有机溶剂残留

Simultaneous Determination of Six Organic Solvent Residues in the Active Pharmaceutical Ingredients of Sorafenib Tosylate by Ionic Liquid-Headspace Gas Chromatography

目的建立可同时检测甲苯磺酸索拉非尼原料中有机溶剂残留的离子液体-顶空气相色谱法。方法色谱柱为HP-5毛细管色谱柱(30 m×0.32 mm,1μm),载气为氮气,检测器为火焰离子化检测器,检测器温度为220℃,进样口温度为200℃,程序升温,溶剂为1-丁基-3-甲基咪唑四氟硼酸盐离子液,进样方式为顶空进样。结果乙醇、丙酮、二氯甲烷、乙酸乙酯、四氢呋喃和N,N-二甲基甲酰胺(DMF)质量浓度分别在0.01~1.0 mg/m L,0.01~1.0 mg/m L,0.0012~0.12 mg/m L,0.01~1.0 mg/m L,0.0014~0.14 mg/m L,0.0018~0.18 mg/m L(r均大于0.992)范围内与峰面积线性关系良好;检测限分别为0.67,0.57,1.21,0.52,0.47,12.20μg/m L,定量限分别为2.0,1.9,3.8,1.6,1.4,38.2μg/m L;精密度试验的RSD值分别为0.53%,0.50%,3.25%,0.85%,1.71%,3.82%(n=6);平均加样回收率分别为93.33%,98.78%,91.13%,94.48%,90.93%,90.39%,RSD分别为1.91%,0.66%,1.07%,0.52%,1.27%,1.16%(n=9)。结论采用离子液体作为溶剂,操作简便、检测限低、结果准确、重复性好,可用于多种溶剂残留的同时测定,扩展了顶空气相色谱法在药物有机溶剂残留测定中的应用范围。

Objective To establish an ionic liquid-headspace gas chromatography method for the simultaneous determination of organic solvent residues in the active pharmaceutical ingredients(API)of sorafenib tosylate.Methods The chromatographic column was HP-5 capillary column(30 m×0.32 mm,1μm),the carrier gas was nitrogen,the detector was flame ionization detector(FID)with the temperature of 220℃,the injection port temperature was 200℃with temperature-programmed,the solvent was 1-butyl-3-methylimidazolium tetrafluoroborate ionic liquid,and the sampling method was headspace injection.Results The linear ranges of ethanol,acetone,dichloromethane,ethyl acetate,tetrahydrofuran and N,N-dimethylformamide(DMF)were 0.01-1.0 mg/m L,0.01-1.0 mg/mL,0.0012-0.12 mg/m L,0.01-1.0,0.0014-0.14 mg/m L,0.0018-0.18 mg/m L(r>0.992),their limits of detection(LOD)were 0.67,0.57,1.21,0.52,0.47 and 12.20μg/m L,respectively,and the their limits of quantitation(LOQ)were 2.0,1.9,3.8,1.6,1.4 and38.2μg/m L,respectively.The RSDs of their precision tests were 0.53%,0.50%,3.25%,0.85%,1.71%and 3.82%(n=6),respectively.The average recoveries of ethanol,acetone,dichloromethane,ethyl acetate,tetrahydrofuran and DMF were 93.33%,98.78%,91.13%,94.48%,90.93%,90.39%with RSDs of 1.91%,0.66%,1.07%,0.52%,1.27%and 1.16%(n=9),respectively.Conclusion The method with ionic liquid as solvent has the advantages of simple operation,low detection limit,accurate results and good reproducibility,which can be used for the simultaneous determination of various solvent residues,and further expands the application scope of headspace gas chromatography in the determination of organic solvent residues in drugs.