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

关键词:  奥美沙坦酯  基因毒性杂质  高效液相色谱法

Key words:  Olmesartan Medoxomil  genotoxic impurity  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，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-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 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.