摘要
目的建立液相色谱-串联质谱联用(LC-MS/MS)法测定替格瑞洛中基因毒性杂质N,N-二乙基苯胺。方法采用色谱柱Ultimate®UHPLC XB-Phenyl(2.1 mm×100 mm,1.8μm);流动相A为0.1%甲酸水溶液,流动相B为0.1%甲酸的甲醇溶液,梯度洗脱,流速为0.3 ml/min,柱温为40℃;采用AB SCIEX ExionLC-QTRAP5500三重四级杆串联离子阱液质联用仪,电喷雾离子源(ESI+)、以监测模式为多反应监测模式(Multiple Reaction Monitoring,MRM)二级质谱MS/MS,定量离子对为150.2→160.0(m/z,Da)进行检测。结果N,N-二乙基苯胺在0.20~15.80 ng/ml浓度范围内呈良好线性关系,线性方程为y=1360211.0060 x+62126.0011(r=0.9999);检测限为0.06 ng/ml;定量限为0.2 ng/ml。平均加样回收率95.3%,RSD=0.84%(n=9)。结论该方法简便准确可靠,可用于替格瑞洛原料药中N,N-二乙基苯胺的含量测定。
Objective To establish a liquid chromatography-mass s p e c t r ome t r y(L C-MS/MS)f o r t h e determination of genotoxic impurities N,N-diethylaniline in ticagrelor.Methods Ultimate®UHPLC XB-Phenyl column(2.1 mm×100 mm,1.8μm)was used.The mobile phase A was aqueous solution of 0.1%formic acid and mobile phase B was methanolic solution of 0.1%formic acid,the gradient elution was performed at a flow rate of 0.3 ml/min and a column temperature of 40℃.The AB SCIEX ExionLC-QTRAP5500 triple quadrupole tandem ion trap liquid mass spectrometer,electrospray ionization source(ESI+),secondary mass spectrometer with multiple reaction monitoring(MRM)mode,and quantitative ion pair of 150.2→160.0(m/z,Da)were used for the detection.Results N,N-diethylaniline showed a good linear relationship in the concentration range from 0.20 to 15.80 ng/ml,and the linear equation was y=1360211.0060 x+62126.0011(r=0.9999).The detection limit was 0.06 ng/ml,and the limit of quantitation was 0.2 ng/ml.The average spiked recovery was 95.3%with RSD=0.84%(n=9).Conclusion This method is simple,accurate and reliable,and can be used for the determination of N,N-diethylaniline content in ticagrelor.
作者
王庆鹏
陈晓英
骆献丽
李原
刘山崎
张明辉
WANG Qingpeng;CHEN Xiaoying;LUO Xianli;LI Yuan;LIU Shanqi;ZHANG Minghui(Lepu Pharmaceuticals Co.,Ltd.,He'nan,Zhengzhou 450000,China)
出处
《中国医药科学》
2021年第21期79-82,共4页
China Medicine And Pharmacy
关键词
N
N-二乙基苯胺
基因毒性杂质
替格瑞洛
液质联用
N,N-diethylaniline
Genotoxic impurities
Ticagrelor
Liquid c hromatography-mass spectrometry
