HPLC测定奥美沙坦酯中的基因毒性杂质

    Determination of Genotoxic Impurity in Olmesartan Medoxomil by HPLC

    • 摘要: 目的 建立HPLC测定奥美沙坦酯中潜在的基因毒性杂质杂质1N-(三苯基甲基)-5-(4'-溴甲基联苯-2-基)四氮唑,杂质2N-三苯甲基-5-(4',4'-二溴甲基联苯-2-基)四氮唑的含量和限度。方法 采用Phenomenex C18柱(250 mm×4.6 mm,5 μm);流动相:0.1%冰乙酸水溶液-0.1%冰乙酸乙腈溶液(15:85);检测波长:254 nm;流速:1.5 mL·min-1;柱温:25℃。结果 杂质1 和杂质2 均在0.030 97~0.247 7 μg·mL-1内线性良好(r分别为0.999 6和0.998 7),平均回收率分别为94.37%和94.43%,RSD分别为2.38%和2.72%(n=9)。结论 该方法专属性强,准确、灵敏,可以作为奥美沙坦酯中基因毒性杂质1 和杂质2 的液相分析方法。

       

      Abstract: OBJECTIVE To establish a method of HPLC to determine the limit and content of potential genotoxic impurities:N-(triphenylmethyl)-5-(4'-bromomethylbiphenyl-2-yl-) tetrazole (impurity 1), and N-(triphenylmethyl)-5-4',4'-(dibromomethylbiphenyl)-2-yltetrazole (impurity 2) in active pharmaceutical substance Olmesartan Medoxomil qualitatively and quantitatively. METHODS The method was performed on Phenomenex C18 column (250 mm×4.6mm, 5 μm). And 0.1% glacial acetic acid in water (A):0.1% glacial acetic acid dissolved in acetonitrile (B) as the mobile phase which was 15:85 with a flow rate at 1.5 mL·min-1. The detection wavelength was 254 nm, and the temperature of column was 25℃. RESULTS The calibration curve for impurity 1 and impurity 2 was well linear in the range of 0.030 97-0.247 7 μg·mL-1(rwas 0.999 6 and 0.998 7, respectively). Average recovery for impurity 1 and impurity 2 was 94.37% and 94.43%, and RSD was 2.38% and 2.72%(n=9), separately. CONCLUSION The method is highly specific, accurate and sensitive, it can be used for the quality control of the genotoxic impurities 1 and impurities 2 of Olmesartan Medoxomil.

       

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