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×3 0 m，0.25 μm)、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。
Abstract
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.
关键词
N- 亚甲基二甲胺 /
盐酸二甲双胍 /
气相色谱- 质谱联用 /
基因毒性杂质
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Key words
N-Nitrosodimethylamine /
metformin hydrochloride /
GC-MS /
genotoxic impurity
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参考文献
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