Abstract:A ultra performance liquid chromatography-hybrid triple quadrupole linear ion-mass spectrometric method(UPLC-QqQLIT) was established for determination of 8 penicilins ( penicillin G, ampicillin, penicillin V, amoxicillin, nafcillin, cloxacillin, oxacillin and dicloxacillin ) and their penicilloic acids (penicilloic acid G , ampicilloic acid, penicilloic acid V, amoxicilloic acid, nafcilloic acid, cloxacilloic acid, oxacilloic acid and dicloxacillioic acid) in milk products. The 8 penicilins and there penicilloic acids in milk products were surveyed.Methods The 8 penicilins and penicilloic acids in milk products were extracted by water in super-sonic instrument, proteins were precipitated by acetonitrile and degreased fat by n-hexane with liquid-liquid extraction, then the purified solution was concentrated by nitrogen, dissolved with acetonitrile-water (10∶90, V/V) and cleaned by 0.22 μm millipore filter. The filtrate was detected by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), identified by electrospray ionization (ESI) in positive mode using multiple reaction monitoring, and quantified with external standards. Information dependent acquisition scan function (IDA) combined with enhanced production scan (EPI) was used to confirm the 8 penicilins and their penicilloic acids. Results The calibration curves of 8 penicilins and penicilloic acids showed good linearity in the range of 1.0-200 μg/L with correlation coefficients of 0.999 1-0.999 9. The detection limits of the method were 0.01-0.05 μg/kg for milk powder and 0.002-0.010 μg/kg for liquid milk. The recoveries of three spiking levels ranged from 80.0% to 110.0%, and the relative standard deviations (RSD) were 0.16%-7.06%.Conclusion The method for determination of 8 penicilins and penicilloic acids in milk products by UPLC-QqQLIT was of operation convenience, less interference from impurities and good accuracy, which could meet the requirements for the determination of 8 penicilins and penicilloic acids residues in milk products.