Abstract: OBJECTIVE To establish a simultaneous determination method of five sulfonate esters of genotoxic impurities(methyl methanesulfonate, ethyl methanesulfonate, methanesulfonicacid, 1-methylethylester, propyl methanesulfonate, N-butyl methanesulfonate) in safinamide. METHODS HS-GC-MS with online derivative method was conducted. The column was RESTEK sil Rxi-624 capillary column(30 m×0.25 mm, 1.4 μm). Detector was a mass spectrometer detector, ionization mode was electron impact(EI), collection mode was selection monitoring. RESULTS The detection limit of 5 impurities were 0.3-1.3 ng·mL^-1, quantitative limit were 0.9-4.3 ng·mL^-1. The RSDs of precision, stability and reproducibility tests were all <5%. Within the concentration range of 5-300 ng·mL^-1, the peak area of the 5 impurities had a good linear relationship with the corresponding concentration, and the correlation coefficient (r²) were all >0.995. The recovery rates were 99.4%-100.6% and RSD were 0.8%-2.6%(n=9). CONCLUSION The method is simple, reproducible, accurate, and can be used for the determination of sulfonate esters of genotoxic impurities in safinamide.