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
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Key words
UHPLC-MS /
positive/negative ionization switching /
dabigatran etexilate /
toxic impurities /
bromoacetic acid /
4-aminobenzonitrile
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中图分类号:
R927
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参考文献
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