Abstract: The four species of drugs residues in meat were determined by solid phase extraction and ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) with isotopes dilution. This method enabled the comprehensive screening for more than 50 drugs including quinolones, sulfonamides, nitroimidazoles and penicillin. The samples were extracted with the mixed solution of Na-2EDTA-Mcllvaine and acetonitrile， which volume ratio was 7∶3, a step for clean-up and proconcentration of the analytes by MCX solid phase extraction cartridge. The target analytes were separated by Waters C18 column with gradient elution using acetonitrile and 0.1% formate in water as mobile phases. The analytes were detected by positive electrospray ionization with multiple reaction monitoring (MRM). Internal standard method was used to determine the results. In the linear range of 5—200 μg/L for each drugs, the correlation coefficient is greater than 0.99 for each antibiotics. The limit of detection (LOD) is 0.5—2.0 μg/kg, and the limit of quantitation (LOQ) is 2.0—6.5 μg/kg. The mean recoveries at the three spiked levels of 10， 50，100 μg/kg are 70.0%—130.9%. The relative standard deviation (RSD) of intra-day and inter-day are 1.03%—9.86%. The proposed method was successfully applied to the analysis of real samples and trace of sulfamethazine and sulfadimoxine were detected in three samples. Identification of the positive samples is based on accurate mass measurement by liquid chromatography-ion trap-time of flight tandem mass spectrometry. The method simplify, sensitivity and good precision， wich can be suitable for determination and confirmation of drugs residues in meat.