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A method of ultra high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) combined with modified QuEChERS purification technology was developed for the simultaneous determination of 25 veterinary medicine residues including four classes (sulfonamides, quinolones, chloramphenicols and amantidines) in chicken and egg. The samples were hydrolyzed by dilute hydrochloric acid, extracted by acetonitrile. Sodium chloride was added into the extracting solution to salt out. The acetonitrile was took out and degreased by n-hexanecyclohexane solution (1∶1,V/V) after stratification of acetonitrile and aqueous phase and concentrated to dry. The residues were dissolved with 0.2% formic acid ethyl acetate to remove the sodium chloride by filtrating and the filtrate was concentrated to dry again, then the sample was purified with a mixture of 30 mg of C18 and 60 mg PSA after adding 0.2% formic acid methanol. The target compounds were separated by ZORBAX C18 chromatography column (50 mm×2.1 mm×1.8 μm), the mass spectrometer data were acquired under multiple reaction monitoring (MRM) of positive and negative modes at the same time, and the residues were quantitated by isotope internal standard method. The results showed that the linear of 25 veterinary medicines is good in the range of 0.2~250 μg/L. The linear correlation coefficients are more than 0.99, and the detection limits are in the range of 0.1~0.9 μg/kg. The limits of quantification are 0.3~3.0 μg/kg. The average recoveries at three spiked levels (about 1, 5 and 20 folds of quantitative limits) are 79.5%~119% with the relative standard deviations of 0.9%~9.2%. The method is rapid,simple, accurate, sensitive and cheap, which is suitable for simultaneous determination of multiple vererinary medicine residues in eggs and chicken.