UPLC-MS/MS法测定厄贝沙坦原料药中8种亚硝胺杂质  

Determination of Eight N-nitrosamine Impurities in Irbesartan by UPLC-MS/MS

作　　者：彭燕 杨云帆 赵兰玲 杜金蔚 林妮妮 董颖 PENG Yan;YANG Yun-fan;ZHAO Lan-ling;DU Jin-wei;LIN Ni-ni;DONG Ying(Beijing Leadingpharm Medical Technology Development Co.,Ltd.,Beijing 100094,China)

机构地区：[1]北京新领先医药科技发展有限公司,北京100094

出　　处：《中国药物评价》2022年第3期199-203,共5页Chinese Journal of Drug Evaluation

摘　　要：目的:建立同时测定厄贝沙坦原料药中8种亚硝胺化合物的超高效液相色谱-串联质谱(UPLC-MS/MS)方法。方法:采用Waters XBridge C_(18)色谱柱(4.6 mm×150 mm,5μm),以0.1%甲酸水(A)-甲醇(B)为流动相,梯度洗脱,流速1.0 mL·min^(-1),柱温40℃,进样体积40μL;质谱离子源为APCI,正离子模式,多反应监测(MRM)采集。结果:该方法的检测限和定量限范围分别在0.07~1.02 ng·mL^(-1)和0.25~3.41 ng·mL^(-1)之间。8种亚硝胺化合物浓度在0.25~23.87 ng·mL^(-1)范围内,线性关系良好,r^(2)>0.99;回收率(n=9)平均值为85.9%~104.9%,RSD值为14.19%~21.01%;重复性RSD值为3.51%~11.09%,中间精密度RSD值为8.52%~19.96%。结论:本方法专属性强、灵敏度高,可用于测定厄贝沙坦原料药中8种亚硝胺杂质的含量,为其原料药质量控制提供数据支持。Objective:To establish a specific method for simultaneous determination of eight N-nitrosamine impurities in irbesartan using UPLC-MS/MS technique.Methods:The separation was performed on a Waters XBridge C_(18) column(4.6mm×150mm,5μm)with the mobile phase consisting of 0.1%formic acid aqueous solution(mobile phase A)and methanol(mobile phase B)by gradient elution at the rate of 1.0 mL·min^(-1).The column temperature was 40℃.Multiple reaction monitoring(MRM)was performed on a triple quadrupole mass spectrometer equipped with APCI source in positive mode for the quantitative detection of eight N-nitrosamine impurities with injection volume of 40μL.Results:The limit of detection(LOD)and limit of quantification(LOQ)were between 0.07-1.02 ng·mL^(-1) and 0.25-3.41 ng·mL^(-1) respectively.The calibration curve was linear(r 2>0.99)over the concentration range of 0.25-23.87 ng·mL^(-1) for eight compounds.The method also afforded satisfactory results in terms of recoveries(n=9,85.9%-104.9%,RSD14.19%-21.01%),intra-and inter-day precisions(3.51%-11.09%and 8.52%-19.96%separately).Conclusion:The developed method has been employed to determinate eight N-nitrosamine impurities and control the quality of irbesartan due to its sensitivity and accuracy.

关 键 词：基因毒性杂质 N-亚硝胺类化合物 厄贝沙坦 超高效液相色谱-串联质谱 

分 类 号：R927.2[医药卫生—药学]