关键词: font-size:medium, ">遗传毒性杂质； 超高效液相色谱串联三重四极杆质谱法； 坎地沙坦酯； 含量测定； 2-(叔丁氧基羰基)氨基-3-硝基苯甲酸乙酯； 2-氰基-4′-溴甲基联苯； 2-[（2-氰基联苯-4-基）甲基]氨基-3-硝基苯甲酸乙酯

Abstract: Objective： To establish an UPLC-MS/MS method for the rapid determination of three genotoxic impurities， 2-((tert-butoxy-carbonyl) amino-3-nitrobenzoate， 2-cyano4 ′-bromo-methyl biphenyl and 2-[[(2-cyanobiphenyl-4-yl) methyl] amino]-3-nitrobenzoate in candesartan cilexetilraw materialsand tablets. Methods： The chromatography was performed on Waters CortecsT3 column （2.1 mm×100 mm， 2.7 μm).Acetonitrile-0.1% formic acid aqueous solution（55∶45) was used as the mobile phase at a flow rate of 0.5 mL·min-1.The column temperature was 30 ℃，Sample size 5 μL. The mass spectrometry was quantitatively analyzed by electrospray（ESI) ion source and multiple reaction monitoring（MRM) positive ion detection mode. Results： The 3 kinds of target impurities were all in the concentration range of 0.1-2.0 μg·mL-1（equivalent to 0.002%-0.04% of the principal component.The 3 target impurity limit was 0.02%， the total limit was 0.06%) and the peak area had a good linear relationship（r≥0.999 1). The average recoveries were 98.6-107.5% and RSD were 0.3-2.2%. The detection limits were 0.000 4-0.15 ng·mL-1， and the limits of quantification were 0.001-0.51 ng·mL-1， respectively， which basically met the detection sensitivity requirements of target impurities. After inspection， the contents of 3 kinds of impurities in 6 batches of samples did not exceed the limit of quantitative concentration， and all met the regulations. Conclusion： The method is simple， sensitive and accurate， with a linear response within the specified limit， and the analysis time is as short as 8 min， which can provide a reference for the study of such impurities in other drugs.

Key words: font-size:medium, ">Genotoxic impurities； UPLC-MS/MS； Candesartan cilexetil； Content determination； 2-((tert-butoxycarbonyl) amino)-3-nitrobenzoate； 2-cyano-4′-bromomethyl biphenyl； 2-[[(2-cyanobiphenyl-4-yl) methyl] amino]-3-nitrobenzoate