Abstract:This study aimed to develop a method for the simultaneous determination of β-agonists，quinolones，and sulfonamides in raw milk by quick，easy，cheap，effective，rugged and safe（QuEChERS）extraction and high performance liquid chromatography-tandem mass spectrometry（HPLC-MS/MS）.The drug residues were extracted with acid acetonitrile and ethylene diamine tetraacetic acid-Mcllvaine buffer solution.The acetonitrile extract was desalted，purified by dispersive solid phase extraction with n-octadecylsilane and primarysecondary amine，and finally analyzed by HPLC-MS/MS in multiple reaction monitoring（MRM）mode via positive-ion electrospray ionization.Good linearity was obtained for the 30 analytes within the concentration range of 0.5 μg/kg-100.0 μg/kg，with the correlation coefficients（r）higher than 0.99.The limit of detection and the limit of quantification of the 30 veterinary drugs were 0.10 μg/kg-1.21 μg/kg and 0.28 μg/kg-4.05 μg/kg，respectively.The recoveries of these compounds varied within 71.1%-94.8%at the levels of 5.0 ，10.0 μg/kg and 20.0 μg/kg，and the reproducibility represented by relative standard deviation was below 12.2%.The method was reliable for determining the residues of 30 veterinary drugs in raw milk with high accuracy and sensitivity.