LC-MS/MS法测定噻托溴铵中的杂质G和杂质H  

Determination of impurities G and H in tiotropium bromide by LC-MS/MS

作　　者：郜继东 王立萍[1] 李洁[1] 刘英[1] GAO Jidong;WANG Liping;LI Jie;LIU Ying(Henan Provincial Institute for Food and Drug Control,Zhengzhou 450018,China)

机构地区：[1]河南省食品药品检验所,郑州450018

出　　处：《中国药品标准》2022年第6期624-628,共5页Drug Standards of China

摘　　要：目的:采用LC-MS/MS法测定噻托溴铵中的杂质G和杂质H。方法:采用Agilent ZORBAX 300-SCX(3.0 mm×50 mm,5μm)色谱柱;流动相为0.05 mol·L^(-1)乙酸铵溶液(用冰醋酸调pH至4.0)-乙腈(10∶90),用电喷雾离子化四极杆串联质谱,以多反应监测方式进行正离子扫描检测。结果:杂质G在0.1711~0.8554μg·mL^(-1)浓度范围内呈良好线性关系,r=0.998;在低、中、高浓度下的加样回收率均值为102.0%,RSD为2.7%(n=9);杂质H在0.1555~0.7777μg·mL^(-1)浓度范围内呈良好线性关系,r=0.996;在低、中、高浓度下的加样回收率均值为103.7%,RSD为4.6%(n=9)。按S/N=10计算,杂质G定量限为1.4×10^(-3) ng,杂质H定量限为1.2×10^(-3) ng。3批次样品均未检出杂质G和杂质H。结论:本法可用于噻托溴铵中杂质G和杂质H的定量检测,并为噻托溴铵质量标准提供参考。Objective:Impurities G and H in tiotropium bromide were determined by LC-MS/MS.Methods:Agilent ZORBAX 300-SCX(3.0 mm×50 mm,5μm)column was used.The mobile phase consisted of 0.05 mol·L^(-1) ammonium acetate solution(pH adjusted to 4.0 by glacial acetic acid)and acetonitrile(10∶90).The multiple reaction monitoring was performed in the positive electrospray ionization mode.Results:Impurity G showed a good linear relationship between 0.1711 and 0.8554μg·mL^(-1)(r=0.998).The average recovery was 102.0%with RSD of 2.7%(n=9)at low,medium and high concentrations.Impurity H presented a linear relationship in the range of 0.1555μg·mL^(-1) to 0.7777μg·mL^(-1)(r=0.996).The average recovery was 103.7%with RSD of 4.6%(n=9)at low,medium and high concentrations.According to S/N=10,the quantitative limit of impurities G and H were 1.4×10^(-3) ng and 1.2×10^(-3) ng,respectively.Impurities G and H were not detected in three batches of samples.Conclusions:This method can be used for the quantitative determination of impurities G and H in tiotropium bromide,which provides a reference for the quality standard of tiotropium bromide.

关 键 词：噻托溴铵 M受体拮抗剂 杂质G 杂质H LC-MS/MS 

分 类 号：R921.2[医药卫生—药学]