A comprehensive method was developed for the simultaneous analysis of 50 antibiotic drugs,including chloramphenicol,sulfonamides,fluoroquinolones,tetracyclines and macrolides in sewage sludge by ultra performance liquid chromatography-tandem mass spectrometry（UPLC-MS/MS）.The sludge samples were ultrasonically extracted with acetonitrile-water solution and then centrifugated.The supernatant were concentrated with an Oasis HLB solid-phase extraction（SPE） cartridge and purified with an amino SPE cartridge.The separation of 50 target drugs was performed on an ACQUITY UPLC BEH C18 column using a mobile phase of 0.1% formic acid-methanol（ESI+） or acetonitrile-water（ESI-）by gradient elution.A multiple reaction monitoring（MRM）was employed in mass spectrometry acquisition.The matrix matched external standard calibration was used for quantitation.Good linearities of the analytes were achieved over the concentration of 0.50-400 μg/L,with correlation coefficients above 0.99.The method quantitation limits（MQL）for target compounds were in the range of 0.10-5.00 μg/kg.Average recoveries of 50 analytes at three spiked levels ranged from 40% to 111% with relative standard deviations（RSDs）of 2.9%-27.1%.The developed method was applied in the analysis of target drugs in both activated and excess sludge samples from sewage treatment plants in Beijing,while 14 target compounds,namely sulfadiazine, sulfapyridine,sulfamethoxazole,pipemdilic acid,ofloxacin,enoxacin,pefloxacin,norfloxacin,ciprofloxacin,enrofloxacin,lomefloxacin,sparfloxacin,oxytetracycline and azithromycin,were detected in the concentration range of 1.2-442.5 μg/kg.The method was rapid,sensitive and reliable,and was suitable for the simultaneous determination of 50 antibiotics in sludge sample.