Abstract: Kinds of 16 sulfonamides (sulfadimethoxine, sulfamonomethoxine, sulfaphenazole, sulfamethazine, sulfamethoxypyridazine, sulfameter, sulfapyridine, sulfadoxin, sulfamerazine, sulfathiazole,sulfamethoxazole, sulfadiazine, sulfachloropyridazine, sulfisoxazole, sulfamethizole, sulfacetamide ) in tooth paste were determined by liquid chromatography tandem mass spectrometry. The sample were extracted under ultrasonication. Qualitative and quantitative analysis were carried out by mass spectrometry under the MRM mode after the chromatographic separation on Agilent poroshell 120 SB-C18（3.0 mm×100 mm×2.7 μm）column. The limits of detection for the 16 sulfonamides are 2.0 mg/kg. The mean recoveries at the three spiked levels are 81.2%—104.7%， and the relative standard deviation is less than 9.1%. This method is simplify, sensitive and accurate，which is suitable for investigation of sulfonamides residues in tooth paste.