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A sensitive method was developed for the determination of residue of 5 cephalothins in honey by high performance liquid chromatography coupled with electrospray tandem mass spectrometry (HPLC-MS/MS). Honey sample was dissolved in sodium dihydrogen phosphate buffer solution, then sample solution was cleaned up with Oasis HLB SPE cartridge. Identification was achieved by electrospray ionization(ESI) in positive mode. The target compounds were separated on a C18 column by gradient elution with acetonitrile and 0.1% formic acid solution as mobile phase and residues were quantified in multiple reaction monitoring mode. Recoveries of 5 cephalothins were between 84.2% and 102.5% (n = 10) at spiked levels of 2.0-100.0 mu g/kg. The relative standard deviations(RSD) of the method were between 3.89% and 9.08%. The limit of quantitation(LOQ) of the method for cefazolin was 10.0 mu g/kg, and the LOQ of the method for cephapirin, cephalexin, cefalonium and cefquinome was 2.0 mu g/kg.