GC-MS法测定磷酸西格列汀中磷酸三甲酯的含量

Determination of Trimethyl Phosphate in Sitagliptin Phosphate by GC-MS

建立了气相色谱-质谱(GC-MS)法测定磷酸西格列汀(1)中的基因毒性杂质磷酸三甲酯(3)。色谱柱选用DB-624(0.25 mm×30 m×1.4 μm)毛细管柱,采用选择离子监测(SIM)模式。结果显示,3在40.93~233.90 ng/ml内线性关系良好,定量限为40.9 ng/ml,检测限为12.3 ng/ml,平均加样回收率(n=12)为97.0%,RSD为5.2%,且稳定性良好。样品检测结果显示3批1中均未检出3,建立的分析方法重复性好、专属性强、灵敏度高,适用于1中基因毒性杂质3的检测。

A gas chromatography-mass spectrometry(GC-MS) method was established for the determination of the genotoxic impurity trimethyl phosphate(3) in sitagliptin phosphate(1).The DB-624(0.25 mm×30 m×1.4 μm) capillary column was used,and the selected ion monitoring(SIM) mode was adopted.The results showed that it was linear for 3 in the range of 40.93-233.90 ng/ml,the limit of quantification was 40.9 ng/ml,and the limit of detection was 12.3 ng/ml.The average sample recovery(n=12) was 97.0%,with the RSD of 5.2%,and the stability was good.The sample test results showed that 3 was not detected in three batches of 1.The established method has good repeatability,strong specificity and high sensitivity,which is suitable for the detection of genotoxic impurity 3 in 1.