Determination of Genotoxic Impurity in Olmesartan Medoxomil by HPLC

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.