Abstract:An analytical method was established for the simultaneous determination of 48 veterinary drug residues in chicken by high performance liquid chromatography coupled with quadrupole-time of flight mass spectrometry（UPLC-Q-TOF/MS）. The samples was extracted with acetonitrile and water（7∶3， volume ratio）， and determined by UPLC-Q-TOF/MS after cleaned-up by solid phase extraction with a Oasis PRiME HLB car－ tridge. The target compounds was quantified by external standard method with acquisition under positive ion mode was performed to obtain accurate relative molecular masses. A date base containing the accurate mass numbers and a library which contains the 48 veterinary drugs were established. According to the characteristics of accurate mass， retention time and so on， the qualitative identifications of 48 veterinary drugs were accom－ plished without the contrast of standard substances. The results showed that the calibration curves were linear in the range of 3.0 μg/L-300 μg/L for 48 veterinary drugs with correlation coefficient （r） more than 0.99. The lim its of quantitation （LODs， S/N=10）were in the range of 3.0 μg/kg-30 μg/kg. The method was sensitive， conve－ nient and accurate， and could satisfy the demand of detection and analysis of veterinary drug residues in chicken.