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An analytical method was established for the simultaneous determination of 42 pesticides and veterinary drugs in milk by ultra performance liquid chromatography coupled with quadrupole-time of flight mass spectrometry (UPLC-Q-TOF-MS). The target compounds are the commonly used drugs including 13 pesticides and 29 veterinary drugs. The QuEChERS (Quick, Easy, Cheap, Effective, Rugged, and Safe) method was used for sample preparation. The analytes in milk samples were extracted with acetonitrile containing 1.0% (v/v) formic acid, and were salted out by adding anhydrous sodium sulfate and potassium chloride. After that, the extract solution was purified by dispersive solid phase extraction with C18 sorbent. In the chromatographic analysis of 42 target compounds were separated on an ACQUITY UPLC BEH C18 column with the gradient elution using the mobile phases of acetonitrile and water containing 0.1% formic acid. MS(E) (where E represents collision energy) acquisition under positive ion mode was performed to obtain accurate relative molecular masses and fragment ions. As a result, the limits of quantification (LOQ, S/N = 10) of the target compounds were from 1 microg/kg to 100 microg/kg in milk. The average recoveries of the 42 analytes spiked at three concentration levels were ranged from 68.2% to 129.1% with the relative standard deviations of 2.8% - 30.8%. This method can be applied to the analysis of the 42 pesticides and veterinary drugs in milk due to its fastness, simplicity and relatively high sensitivity.