A highly selective and sensitive analytical method was developed for simultaneous determination of three classes of commonly used antibiotics，including five sulfonamides，three tetracyclines and one macrolide in the activated sludge of municipal sewage treatment plants（STPs） by ultrasonic extraction，solid phase extraction and high performance liquid chromatography-mass spectrometry （LC-MS）. The activated sludge sample was ultrasonically extracted with a mixture of methanol and Na2EDTA／McIlvaine buffer（1∶1），then concentrated and purified with an HLB cartridge. The separation of targeted compound was performed with a Waters Symmetry C18 column using 0.2% formic acid（A）-acetonitrile（B） as mobile phase. The qualification and quantification of the selected antibiotics were carried out by MS with an electrospray ionization（ESI） under the positive ion mode. The method showed good linearity（r2 > 0.99） for the antibiotics concentration in the range of 0.001-1 mg／L. The recoveries at three spiked levels were in the range of 80%-108% for sulfonamides（SAs），91%-112% for tetracyclines（TCs） and 50%-59% for tiamulin（TIA）. The inter day and intra day relative standard deviations were no more than 7.4% and 13.7%，respectively. The limits of detection（LOD） were between 1 μg/kg and 16 μg/kg. The developed method was applied in the detection of the activated sludge samples collected from two STPs located in Beijing and five target antibiotics were detected with concentrations of 124.9-523.3 μg/kg for sulfanomindes and 166.5-2 296.4 μg/kg for tetracyclines，respectively.