气相色谱-质谱联用法测定不同厂家盐酸二甲双胍缓释片中N-亚硝基二甲胺的含量

目的：建立气相色谱-质谱联用（gas chromatography-mass spectrometry，GC-MS）法测定不同厂家盐酸二甲双胍缓释片中N-亚硝基二甲胺（N-nitrosodimethylamine，NDMA）的含量。方法：采用GC-MS法，标准曲线法计算盐酸二甲双胍缓释片中NDMA的含量。色谱柱为Agilent VF-WAXms （30 m×0.25 mm，0.25 μm），程序升温，以多反应监测（MRM）模式进行离子检测。结果：该方法线性范围为0.25~50.00 ng·mL^-1，r=0.999 9；平均加标回收率为107.79%，RSD为3.53%；检出限为0.25 ng·mL^-1。采用该方法对市面上31家企业共75批次的盐酸二甲双胍缓释片进行NDMA含量测定，2018年、2019年和2020年批次中均存在一定比例的超限。结论：该方法操作简单、灵敏、准确，适用于盐酸二甲双胍缓释片中NDMA的检测，可为其质量控制提供参考。

Determination of N-nitrosodimethylamine in metformin hydrochloride sustained-release tablets from different manufacturers by gas chromatography-mass spectrometry

OBJECTIVE To establish a GC-MS method to determine the content of N-nitrosodimethylamine (NDMA) in metformin hydrochloride sustained-release tablets to ensure the quality and safety of metformin hydrochloride sustained-release tablets.METHODS The content of NDMA in metformin hydrochloride sustained-release tablets was determined by GC-MS and external standard curve method.The chromatographic column was Agilent VF-WAXms (30 m×0.25 mm,0.25 μm),programmed to heat,and ion detection was performed in multiple reaction monitoring (MRM) mode.RESULTS The linear range of the method was 0.25-50.00 ng·mL^-1,r=0.999 9;the average recovery rate of standard addition was 107.79 %,RSD was 3.53 %,and the limit of detection was 0.25 ng·mL^-1.A total of 75 batches of metformin hydrochloride sustained-release tablets samples from 31 companies were determined using the established method.CONCLUSION The method is simple,sensitive and accurate.It is suitable for the detection of NDMA in metformin hydrochloride sustained-release tablets and provides a reference for its quality control.