气相色谱-质谱联用法测定盐酸二甲双胍及制剂中的痕量N-亚硝基二甲胺

Determination of N-Nitrosodimethylamine in Metformin Hydrochloride and Its Preparations by GC-MS

建立了气相色谱-质谱联用(GC-MS)法测定盐酸二甲双胍及其制剂中基因毒性杂质N-亚硝基二甲胺(NDMA)。采用以聚乙二醇为固定相的毛细管柱(0.25 mm×30 m,0.25μm)、电子轰击(EI)离子源和选择反应监测(SRM)模式,定量离子对为m/z 74→m/z 44(5 eV),定性离子对为m/z 74→m/z 42(15 eV)。结果显示,NDMA的检测限为0.15 ng/ml,定量限为0.5 ng/ml;在0.25~50 ng/ml内,线性关系良好。精密度、重复性、稳定性试验的RSD均小于10%,平均回收率为93.2%~97.9%。本方法灵敏度高、专属性强、结果准确且重现性好,适用于盐酸二甲双胍及其制剂中基因毒性杂质NDMA的含量检测。

An gas chromatography-mass spectrometry(GC-MS)was established to determine the genotoxic impurity N-nitrosodimethylamine(NDMA)in metformin hydrochloride and its preparations.The capillary column(0.25 mm×30 m,0.25 mm)with polyethylene glycol as the stationary phase and an electron impact(EI)ion source were used.The selected reaction monitoring(SRM)mode was adopted.The quantitative ion pair was m/z 74→m/z 44(5 eV),and the qualitative ion pair was m/z 74→m/z 42(15 eV).The results showed that the detection limit of NDMA was 0.15 ng/ml and the quantification limit was 0.5 ng/ml.It was linear for NDMA in the range of 0.25-50 ng/ml.The RSDs of the precision,repeatability,and stability tests were all less than 10%,and the average recovery rate was 93.2%-97.9%.This method has high sensitivity,strong specificity,accurate results and good reproducibility,which is suitable for the determination of the genotoxic impurity NDMA in metformin hydrochloride and its preparations.