A high performance liquid chromatography-quadrupole ion mass spectrometric（HPLC-QTRAP-MS/MS） method was developed for the determination of two potential genotoxic impurities（impurity C and impurity D） residues in dronedarone hydrochloride.After extracted with 0.1% formic acid-acetonitrile（20∶80），the dronedarone hydrochloride samples were separated on an Agilent Extend-C18 column（1.8 μm,2.1 mm×50 mm） or a YMC Pack-CN column（5 μm,46 mm× 250 mm） with two mobile phases of 0.1% formic acid and acetonitrile.The detection of analytes was performed in the positive mode and selective reaction monitoring（SRM） mode.As a result，the calibration curves of impurity C and impurity D showed good linearity in the range of 1.0-50 μg/L.The limits of detection（S/N=3） were 0.20 μg/L and 0.30 μg/L,respectively.The limits of quantitation（S/N=10）were 0.80 μg/L and 1.0 μg/L，respectively.The method has the advantages of simple operation，high sensitivity，good reproducibility，and could be used for the detection of two genotoxic impurities residues in dronedarone hydrochloride.