To screen feed for new or unexpected contaminants at the ppm level,a generic method was developed.The sample was extracted with 0.1%EDTA-acetonitrile-methanol (1∶1∶1,containing 0.1% formic acid) ,and analyzed by high-performance liquid chromatography coupled to electrospray ionization time-of-flight mass spectrometry(HPLC-Q-TOF/MS) in positive ionization mode.The data were collected after peak alignment (mass error within 50 mDa) ,noise filtration,elimination of useless peaks and statistical evaluation was performed based on Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA) .According to the score plot,S-plot and VIP,blind statistical evaluation revealed that feed samples could be separated regarding unknown components by OPLS-DA and the m/z-retention time pair.With the assistance of MS/MS data,isotope abundance ratio,formula generation and self built spectral library,the structures of unknown compounds were confirmed.The results showed that 27 veterinary drugs were screened out from 16 feed samples.By quantitative analysis of 12 existing veterinary drugs using liquid chromatography tandem mass spectrometry(LC-MS/MS) ,only two false positives appeared in the verification results,and the concentration levels of 12 veterinary drugs were between 12.5 mg/kg and 152.0 mg/kg.From the perspective of the results,TOF-MS data and OPLS-DA could be applied in the non-targeted screening of veterinary drugs in feed samples with high accuracy.