顶空气相色谱质谱联用测定厄贝沙坦中遗传毒性杂质N-亚硝基二甲胺和N-亚硝基二乙胺

Determination of n-nitrosodimethylamine and n-nitrosodiethylamine in irbesartan using headspace gas chromatography mass spectrometry

采用顶空进样气相色谱-质谱联用法,对厄贝沙坦原料药中的遗传毒性杂质N-亚硝基二甲胺(NDMA)和N-亚硝基二乙胺(NDEA)进行同时测定。采用岛津SH-Rtx-Wax气相色谱柱程序升温进行分离,电子轰击电离源(EI)电离,选择离子监测(SIM)模式检测。结果表明NDMA和NDEA在10~500 ng/mL浓度范围内线性关系良好,检出限(LOD)分别为1.7 ng/mL和4.5 ng/mL,峰面积相对标准偏差(RSD)均小于2.4%。阴性及阳性样品加标回收率为100.6%~108.7%。该方法能够有效地检测原料药厄贝沙坦中NDMA和NDEA的含量。

A method for determining genotoxic impurities of n-nitrosodimethylamine(NDMA)and nnitrosodiethylamine(NDEA)in irbesartan was established based on gas chromatography-mass spectrometry(GC-MS)with headspace sampling.Samples were separated using Shimadzu SH-Rtx-Wax column under temperature program,ionized by electron ionization(EI),and detected with selected ion monitoring(SIM)data acquisition mode.Results showed that NDMA and NDEA were well correlated with the linearity range between10 ng/m L and 500 ng/m L.Limit of detections(LODs)were 1.7 ng/m L and 4.5 ng/m L for NDMA and NDEA,respectively.Relative standard deviation(RSD)of peak area was lower than 2.4%.The average recoveries were between 100.6%and 108.7%.The established Headspace-GC-MS method is efficient for determining NDMA and NDEA on limit test and quantitation in irbesartan.