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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 C_(18)色谱柱(2.1 mm×50 mm,2μm),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 m L·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·m L~(-1)内线性关系良好(r=0.999 9),定量限为0.1 ng·m L~(-1);对氨基苯腈在0.4~40ng·m L~(-1)内线性关系良好(r=0.999 9),定量限为0.4 ng·m L~(-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。
OBJECTIVE To establish a HPLC-MS method for the determination of 2 bromoacetic acid and p-aminobenzonitrile in dabigatran etexilate intermediates. Methods Shimadzu Shim-Pack GIS C 18 column (2.1 mm × 50 mm, 2 μm) was used. The mobile phase consisted of 0.1% formic acid in water and 0.1% formic acid in methanol as mobile phase. The flow rate was 0.4 m L · min ~ (-1). Using positive and negative ion switching technology, MRM mode for the simultaneous detection of bromoacetic acid and p-aminobenzonitrile. Results The linear range of bromoacetic acid was 0.2 ~ 40 ng · m L -1 (r = 0.999 9), the limit of quantification was 0.1 ng · m L -1, the concentration of p-aminobenzamide was 0.4 ~ 40 ng · The linearity was good (r = 0.999 9) in m L -1, and the limit of quantification was 0.4 ng · m L -1. The recovery of bromoacetic acid was 100.9% and the recovery of p-aminobenzonitrile was 99.6%. Conclusion The established ultra performance liquid chromatography-mass spectrometry method is accurate, rapid, sensitive and reproducible. It can be used in the determination of bromoacetic acid and p-aminobenzonitrile in the intermediate of dabigatran etexilate.