LC-MS/MS法测定厄贝沙坦中基因毒性杂质N-亚硝基二甲胺和N-亚硝基二乙胺

建立同时检测厄贝沙坦中N-亚硝基二甲胺(NDMA)和N-亚硝基二乙胺(NDEA)的液质联用(liquid chromatography-tandem mass spectrometry,LC-MS/MS)方法.选择大气压电离串联四极杆质谱(APCI+MRM)模式进行检测,流动相为0.1％甲酸水溶液-0.1％甲酸甲醇溶液...

Determination of N-nitrosodimethylamine and N-nitrosodiethylamine in irbesartan by liquid chromatography-tandem mass spectrometry

To develop a liquid chromatography-tandem mass spectrometry method for simultaneous detection of N-nitrosodimethylamine(NDMA)and N-nitrosodiethylamine(NDEA)in irbesartan.APCI(+)MRM mode was selected for detection.Gradient elution was conducted with mobile phase consisting of 0.1%formic acid solution and methanol containing 0.1%formic acid.The method had good specificity.Good linearity was obtained for NDMA and NDEA in the range of 1~120 ng·mL^-1and 0.4~48 ng·mL^-1,respectively.The limits of detection(LOD)were 0.5 ng·mL^-1and 0.2 ng·mL^-1for NDMA and NDEA.The relative standard deviation(RSD)of peak area was less than 3.0%.The accuracy was 96.1%~106.2%and repeatability was good.The average percent recovery was 102.5%and 99.9%for NDMA and NDEA,respectively.All samples were stable after being stored for 24 h in auto-injection sampler or at 0℃.This method is simple,sensitive and accurate,and can be used for limit test and quantitation of NDMA and NDEA in irbesartan.