高效液相色谱-三重四极杆/复合线性离子阱质谱法测定厄贝沙坦中的基因毒性杂质

Determination of genotoxic impurities in irbesartan by high performance liquid chromatography-triple quadrupole/linear ion trap mass spectrometry

关键词:  高效液相色谱-三重四极杆/复合线性离子阱质谱  厄贝沙坦  基因毒性杂质

Key words:  high performance liquid chromatography triple quadrupole/linear ion trap mass spectrometry  irbesartan  genotoxic impurities

摘要:

摘要：目的 建立抗高血压药厄贝沙坦中2-氰基-4’-溴甲基联苯和2-氰基-4’, 4’-二溴甲基联苯两种基因毒性杂质的高效液相色谱-三重四极杆/复合线性离子阱质谱分析方法。方法 样品经溶剂溶解后，以Agilent Eclipse XDB-C18 (10×2.1 mm, 3.5 μm)色谱柱分离，梯度洗脱，洗脱液以多反应监测触发增强子离子扫描模式检测，采用二级质谱图进行定性，外标法定量。结果 两种基因毒性杂质检出限和定量限分别为0.5和1.0 mg/kg，在1-20 μg/L范围内线性关系良好（R2>0.999），在1、5、10 μg/L三个加标浓度下，平均回收率在90%-110%之间，相对标准偏差小于5%。结论 该方法操作简便、定性定量准确，能够满足厄贝沙坦中两种基因毒性杂质的分析需求。

Abstract:

ABSTRACT: OBJECTIVE To establish a high performance liquid chromatography-triple quadrupole/linear ion trap mass spectrometry method of two genotoxic impurities, 2-cyano-4""-bromomethyl biphenyl and 2-cyano-4’,4’-bisbromomethyl biphenyl, in the antihypertensive drug irbesartan. METHODS After solvent dissolution, the samples were separated by Agilent Eclipse XDB-C18 column (2.1×100 mm, 3.5 μm) , eluted in gradient, and the eluate was detected by multiple reaction monitoring trigger enhancer ion scanning mode, qualitatively by second-level mass spectrometry and quantified by external standard. RESULTS The detection and quantification limits of the two genotoxic impurities were 0.5 and 1.0 mg/kg, respectively, with good linear relationship between 1-20 μg/L (R2> 0.999), at 1, 5 and 10 μg/L, the average recovery was between 90% and 110%, and the relative standard deviation was less than 5%. CONCLUSION The established method is easy to operate, accurate in qualitative and quantitative analysis, and can meet the analysis needs of the two genotoxic impurities in irbesartan.