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

目的建立HPLC测定奥美沙坦酯中潜在的基因毒性杂质[杂质1:N-(三苯基甲基)-5-(4'-溴甲基联苯-2-基)四氮唑,杂质2:N-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,5μm);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 m L·min-1;柱温:25℃。结果杂质1和杂质2均在0.030 97~0.247 7μg·m L^(-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。

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-yl]tetrazole（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 m L·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·m L^-1（r was 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.