HPLC-MS测定奥美沙坦酯中有关基因毒性杂质

栾保磊; 徐新军; 梁桂挺; 游孟梦; 刘国柱

doi:10.11665/j.issn.1000-5048.20190308

HPLC-MS测定奥美沙坦酯中有关基因毒性杂质

1.
中山大学药学院
2.
东阳光药物研究院

基金项目: 广东省科技厅2017年“扬帆计划”引进创新团队(No.2017YT05S029)

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出版历程
- 刊出日期: 2019-06-24

Determination of related genotoxic impurities in olmesartan medoxomil by HPLC-MS

摘要

摘要: 建立一种直接测定奥美沙坦酯中基因毒性杂质5-(4′-溴甲基联苯-2-基)四氮唑和5-(4′-二溴甲基联苯-2-基)四氮唑的液相色谱-质谱联用方法。采用色谱柱Agilent Zorbax Eclipse Plus C₁₈(250 mm×4.6 mm，5 μm)，以0.1%甲酸水溶液-乙腈为流动相；在电喷雾正离子模式下，对m/z 315和m/z 395离子进行选择性监测。5-(4′-溴甲基联苯-2-基)四氮唑和5-(4′-二溴甲基联苯-2-基)四氮唑的质量浓度分别在0.009 4~0.561 0 μg/mL和0.018 2~0.547 5 μg/mL范围内与峰面积呈良好线性关系；定量限分别为9.35和18.25 ng/mL；检测限分别为3.12和6.08 ng/mL；平均回收率分别为96.5%(n=9，RSD=4.8%)和98.0%(n=9，RSD=5.1%)。本法操作简便、专属性好、准确度高，可用于奥美沙坦酯中基因毒性杂质5-(4′-溴甲基联苯-2-基)四氮唑和5-(4′-二溴甲基联苯-2-基)四氮唑的检测。
- 奥美沙坦酯 /
- 液相色谱-质谱联用 /
- 基因毒性杂质 /
- 5-(4′-溴甲基联苯-2-基)四氮唑 /
- 5-(4′-二溴甲基联苯-2-基)四氮唑
Abstract: The aim of this study was to establish a high performance liquid chromatography-mass spectrometry method for the determination of 5-(4′-(bromomethyl)-［1, 1′-biphenyl］-2-yl)- 1H-tetrazole(BBT1)and 5-(4′-(dibromomethyl)-［1, 1′-biphenyl］-2-yl)-1H-tetrazole(BBT2), which are two genotoxic impurities in olmesartan medoxomil. Chromatographic separation was based on an Agilent Zorbax Eclipse Plus C₁₈(250 mm × 4. 6 mm, 5 μm)column using water(containing 0. 1% formic acid)- acetonitrile as mobile phase in gradient elution mode. Mass spectrometry was operated in positive ion mode. Selective ion monitors were set at m/z 315 for BBT1 and at m/z 395 for BBT2. Good linear correlations were observed in the range of 0. 009 4- 0. 561 0 μg/mL(r=0. 998)with the quantification limit at 9. 35 ng/mL and the detection limit at 3. 12 ng/mL for BBT1, and in the range of 0. 018 2- 0. 547 5 μg/mL(r=0. 999)with the quantification limit at 18. 25 ng/mL and the detection limit at 6. 08 ng/mL for BBT2. Furthermore, the average recoveries of the three spiked concentration level were 96. 5%(n=9, RSD=4. 8%)and 98. 0%(n=9, RSD=5. 1%)for BBT1 and BBT2, respectively. The proposed method is simple, specific and accurate, and quite suitable for the determination of BBT1 and BBT2 in olmesartan medoxomil.

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参考文献(15)

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