柱前衍生化顶空气相色谱法同时检测非布司他原料药中3种微量有机酸

Simultaneous Determination of 3 Kinds of Trace Organic Acids in Febuxostat by Headspace GC with Pre-column Derivatization

目的:建立测定非布司他原料药中3种微量有机酸(三氟乙酸、甲酸和乙酸)含量的方法。方法:采用气相色谱法。以浓硫酸-甲醇混合液对有机酸进行柱前衍生化后采用顶空进样法测定5批原料药中的有机酸含量。色谱柱为Supelcowax-10毛细管柱,检测器为氢火焰离子化检测器,气化室温度为160℃,检测器温度为260℃,程序升温,载气为氮气,分流比为10:1,顶空瓶平衡温度为60℃,平衡时间为60min。结果:3种有机酸衍生物达到基线分离,检测浓度线性范围分别为4.190～605.3、3.586～672.5、3.773～667.4μg.mL-1(r≥0.9990),检测限分别为1.25、1.07、1.13μg.mL-1;5批样品中均未检出有机酸。结论:本法准确、快速,可有效地分离、测定非布司他原料药中3种微量有机酸。

OBJECTIVE：To establish a method for the content determination of 3 kinds of trace organic acids in febuxostat,such as trifluoroacetic acid,formic acid and acetic acid.METHODS：GC method was adopted.The pre-column derivatization of organic acids was conducted with the mixture of methanol and H2SO4.Then the content of organic acid in 5 batches of samples were determined by headspace GC.The separation was performed on Supelcowax-10 capillary column with FID as the detector.The injection temperature was 160 ℃,the detector temperature was 260 ℃,with temperature programming.N2 was used as carrier gas and split ratio was 10：1.Vial equilibration temperature was 60 ℃ with equilibration time of 60 min.RESULTS：The baseline resolution was achieved between the derivatives of three organic acids.The linear ranges were 4.190～605.3 μg·mL-1,3.586～672.5 μg· mL-1,3.773～667.4 μg·mL-1（r≥0.999 0）.The detective limits were 1.25,1.07 and 1.13 μg·mL-1 respectively.No organic acid was found in 5 batches of samples.CONCLUSION：The method is accurate and rapid,and can be used for effective separation and content determination of 3 trace organic acids in febuxostat.