顶空气相色谱法测定苯甲酸阿格列汀原料药中3种有机溶剂残留量

Determination of 3 Residual Organic Solvents in Alogliptin Benzoate Raw Materid by Headspace GC

目的：建立检测苯甲酸阿格列汀原料药中甲苯、正丁醇、乙醇残留量的方法。方法：采用顶空气相色谱法。采用氢火焰离子化检测器,色谱柱为6%氰丙基苯基-94%甲基聚硅氧烷毛细管柱,进样口温度为200℃,检测器温度为250℃,分流比为10∶1,流速为1 ml/min,顶空进样,进样量为20μl,程序升温;以外标法计算甲苯、正丁醇、乙醇的残留量。结果：3种有机溶剂在16 min内能完全分离,分离度均大于1.5;甲苯、正丁醇、乙醇的质量浓度分别在22.25~178、125~1 000、125~1 000μg/ml范围内与各自峰面积呈良好的线性关系（r=0.999 8、0.999 6、0.998 7）;精密度试验的RSD≤1.36%;甲苯、正丁醇、乙醇的平均加样回收率分别为98.2%、101.8%、98.90%,RSD分别为0.6%、0.7%、0.9%（n均为9）。结论：该方法操作简便、结果准确,可用于苯甲酸阿格列汀原料药中有机溶剂残留量的控制。

OBJECTIVE：To establish a method for detection of toluene,N-butanol and ethannol in alogliptin benzoate raw material. METHODS：Headspace gas chromatography（GC）and flame ionization detector（FID）detector were used. The column was6% cyanopropyl phenyl-94%methyl polysiloxane capillary column,inlet temperature was 200 ℃,detector temperature was 250 ℃,split ratio was 10∶1,flow rate was 1 ml/min with headspace and temperature programmed. The injection volume was 20 μl. The the organic residual solvents（toluene,N-butanol and ethanol）were calculated by external standard method. RESULTS：Three organic solvents were completely separated within 16 min,and the separation rate was more than 1.5. The linear range were 22.25-178 μg/ml for toluene（r=0.999 8）,125-1 000 μg/ml for N-butanol（r=0.999 6）,125-1 000 μg/ml for ethanol（r=0.998 7）. RSD of precision was lower than 1.36%. Average recovery rates were 98.2%,101.8%,98.9%（RSD were 0.6%,0.7%,0.9%,n=9）. CONCLUSIONS：The method is simple and accurate. It can be used for the control of the residual solvents in alogliptin benzoate raw material.