Abstract: The method for the determination of vancomycin and norvancomycin residue in egg was established based on SPE with ultra performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS). The samples were extracted with mixed solution of 0.1% formic acid,then purified with solid phase extraction(Strata-X-C),determined by UPLC-MS/MS with positive electrospray ionization mode and multiple-reaction monitoring(MRM)and quantified by external standard method. The results showed that the standard calibration curve had good linear behavior in the range from 5.0 to 100.0 μg/L and the relative coefficient was more than 0.999. The limit of detection and quantitation of the method were 2.0 and 5.0 μg/kg,respectively. The spiked recoveries were 85.6%~96.3%,the relative standard deviation was 3.7%~9.2%. The method is sensitive,accurate,and it can meet the demands of quantitative analysis of vancomycin and norvancomycin in egg.