正负离子切换超高效液相色谱-质谱联用法同时测定达比加群酯中间体中的2个毒性杂质

钱建钦, 陈悦

中国药学杂志 ›› 2016, Vol. 51 ›› Issue (11) : 930-934.

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中国药学杂志 ›› 2016, Vol. 51 ›› Issue (11) : 930-934. DOI: 10.11669/cpj.2016.11.014
论著

正负离子切换超高效液相色谱-质谱联用法同时测定达比加群酯中间体中的2个毒性杂质

  • 钱建钦, 陈悦*
作者信息 +

Simultaneous Determination of Two Toxic Impurities in the Intermediate of Dabigatran Etexilate by UHPLC-MS with Positive/Negative Ionization Switching

  • QIAN Jian-qin, CHEN Yue*
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文章历史 +

摘要

目的 建立超高效液相色谱-质谱联用法测定达比加群酯中间体中2个毒性杂质溴乙酸和对氨基苯腈。方法 采用岛津Shim-Pack GIS C18色谱柱(2.1 mm×50 mm,2 μm),以0.1%甲酸水溶液为流动相A,0.1%甲酸甲醇溶液为流动相B,梯度洗脱,流速为0.4 mL·min-1。采用正负离子切换技术,MRM模式对溴乙酸和对氨基苯腈同时进行检测。结果 溴乙酸在0.2~40 ng·mL-1内线性关系良好(r=0.999 9),定量限为0.1 ng·mL-1;对氨基苯腈在0.4~40 ng·mL-1内线性关系良好(r=0.999 9),定量限为0.4 ng·mL-1。溴乙酸的回收率为100.9%,对氨基苯腈的回收率为99.6%。结论 本实验所建立的超高效液相色谱-质谱联用法准确、快速、灵敏、重现性好,可用于达比加群酯中间体中溴乙酸和对氨基苯腈的测定。

Abstract

OBJECTIVE To determine two toxic impurities, namely bromoacetic acid and 4-aminobenzonitrile, in the intermediate of dabigatran etexilate by UHPLC-MS. METHODS The separation was performed on a Shimadzu Shim-Pack GIS C18 column (2.1 mm×50 mm,2 μm) with mobile phase consisting of 0.1% formic acid aqueous solution (A) and 0.1% formic acid methanol (B) by gradient elution at a flow rate of 0.4 mL·min-1. The detection was achieved by triple quadrupole mass spectrometry with rapid polarity switching using MRM mode. RESULTS The calibration curves were linear in the ranges of 0.2-40 and 0.4-40 ng·mL-1 for bromoacetic acid and 4-aminobenzonitrile, respectively. The values of LOQ of bromoacetic acid and 4-aminobenzonitrile were 0.1 and 0.4 ng·mL-1, respectively. The recoveries of bromoacetic acid and 4-aminobenzonitrile were 100.9% and 99.6%, respectively. CONCLUSION The method is accurate, rapid, sensitive, and reliable to determine the two toxic impurities bromoacetic acid and 4-aminobenzonitrile in the intermediate of dabigatran etexilate for quality control.

关键词

超高效液相色谱-质谱联用法 / 正负离子切换 / 达比加群酯 / 毒性杂质 / 溴乙酸 / 对氨基苯腈

Key words

UHPLC-MS / positive/negative ionization switching / dabigatran etexilate / toxic impurities / bromoacetic acid / 4-aminobenzonitrile

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导出引用
钱建钦, 陈悦. 正负离子切换超高效液相色谱-质谱联用法同时测定达比加群酯中间体中的2个毒性杂质[J]. 中国药学杂志, 2016, 51(11): 930-934 https://doi.org/10.11669/cpj.2016.11.014
QIAN Jian-qin, CHEN Yue. Simultaneous Determination of Two Toxic Impurities in the Intermediate of Dabigatran Etexilate by UHPLC-MS with Positive/Negative Ionization Switching[J]. Chinese Pharmaceutical Journal, 2016, 51(11): 930-934 https://doi.org/10.11669/cpj.2016.11.014
中图分类号: R927   

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