Abstract: A method for the determination of genotoxic impurities of 4-chloro-3-nitroanisole and 3-nitro-4-phenoxyanisole in N-(4-acetyl-5-methoxy-2-phenoxyphenyl)methanesulfonamide, the starting material of iguratimod, was established by HPLC. 35% (φ) acetonitrile solution was used to ultrasonically dissolve the test sample in a 50 ℃ water bath, 0.2% (φ) phosphoric acid solution was added, and the mixed solution was placed in an ice water bath to crystallize for ca. 30 min. The supernatant was taken and passed through a 0.45 μm filter membrane, and the filtrate was used for HPLC analysis. Wondasil C₁₈ column was used as the stationary phase, and a mixture of acetonitrile and 0.01 mol·L^-1 phosphate buffer solution (pH 9.0) at various volume ratios was used as mobile phase for gradient elution. Two targets obtained were detected at the wavelength of 222 nm with photodiode array detector. The results showed that the mass concentrations of the 2 targets in the range of 0.03-0.60 mg·L^-1 were linearly related with the corresponding peak areas, with detection limits (3S/N) of 9.97, 10.04 μg·L^-1, respectively. Test for recovery was made on the actual samples by standard addition method, giving values of recovery in the range of 94.5%-104% and 89.0%-104%, respectively. RSDs of the determined values of 2 targets of tests for repeatability (n=6) and intermediate precision (n=12) on the actual samples found were 3.2%, 4.5% (for repeatability test ) and 4.4%, 6.2% (for intermediate precision test), respectively.