A high performance liquid chromatography-quadrupole ion trap mass spectrometric（HPLC-QTRAP-MS/MS）method was developed for the determination of two potential genotoxic impurities residues,ieomeprazole N-oxide（GTI E）and sulfonylate N-oxide（GTI I）in esomeprazole sodium.The esomeprazole sodium drugs were dissolved with 30% acetonitrile-water（volume fraction）,and then separated on an Agela VenusiL MP-C18 column（21 mm×100 mm,3 μm）by gradient elution using water-acetonitrile as mobile phases at a flow rate of 0.2 mL/min,a column temperature of 35 ℃ and an injection volume of 1 μL.The detection of analytes was performed in the negative electrospray ionization mode（ESI-）under multiple reaction monitoring（MRM）mode.As a result,the calibration curves for GTI E and GTI I showed good linearities in the ranges of 1.26-44.8 μg/L and 1.34-45.2 μg/L,with their correlation coefficients of 0.994 7 and 0.992 8,respectively.The limits of detection（S/N=3）and limits of quantitation（S/N=10）of the method were 0.381 and 0.384 μg/L,and 1.26 and 1.34 μg/L,respectively.The spiked recoveries for GTI E and GTI I were in the ranges of 86.3%-87.6% and 85.8%-91.4%,with the relative standard deviations（RSDs）of 1.5%-2.2% and 0.7%-4.0%,respectively.The method has the advantages of simple operation,high sensitivity,good reproducibility,and could be used for the simultaneous detection of two potential genotoxic impurities including GTI E and GTI I in esomeprazole sodium.