OBJECTIVE To establish a chromatography-mass spectrometry method for simultanenous detection of 3 genotoxic impurities in pantoprazole sodium. METHODS The chromatographic column was octadecylsilane bonded silica gel as filler (Kromasil 100-5, 4.6 mm×25 cm, 5 μm or equivalent column), acetonitrile-0.01 mol·L−1 ammonium acetate(35∶65) as mobile phase, flow rate 0.9 mL·min−1, column temperature 25 ℃; positiveion detection mode, scanning range: 150−450 Da, dryer temperature 350 ℃, dry gas flow rate 10 L·min−1, atomization gas pressure 50 psig, capillary voltage 4 000 V, fragmentation voltage 175 V, cone hole voltage 65 V. The time for entering the mass spectrometry was set to 0−3.5 minutes to waste, 3.5 minutes to retain the main peak-0.5 minutes to MS, and 0.5 minutes to end to waste. RESULTS The concentration of genotoxic impurity 1 had a good linear relationship with peak area between 9.04−27.13 ng·mL−1(r=0.998), the concentration of genotoxic impurity 2 had a good linear relationship with peak area between 8.92−26.75 ng·mL−1(r=0.999), and the concentration of intermediate II had a good linear relationship with peak area between 7.78−23.34 ng·mL−1(r=0.990); the quantitative limit of genotoxic impurity 1 was 9.0430 ng·mL−1, and the detection limit was 0.9043 ng·mL−1; the quantitative limit of genotoxic impurity 2 was 8.9174 ng·mL−1, and the detection limit was 2.9725 ng·mL−1; the quantitative limit of intermediate II was 7.7792 ng·mL−1, and the detection limit was 0.7779 ng·mL−1; the recovery rate of 3 genotoxic impurities ranges from 92.3%−107.0%, with an RSD of 2.0%−7.9%. No three impurities were detected in pantoprazole sodium. CONCLUSION This method can accurately and quantitatively determine three genotoxic impurities of pantoprazole sodium raw material: genotoxic impurity 1, genotoxic impurity 2, and intermediate II. The method has strong specificity, high sensitivity, simple and rapid experimental operation, and can be used for the determination of the above three genotoxic impurities in pantoprazole sodium.