Sample extraction, cleanup and analysis methods were developed for the simultaneous determination of multi-class of veterinary drug residues, for examples, tetracyclines, macrolides, amphenicols, quinolones and β-lactam antibiotics in eggs by ultra-performance liquid chromatography coupled to a tandem quadrupole mass spectrometry. Egg samples were treated with an acidified acetonitrile/water solvent to precipitate proteins and to extract seventeen representative compounds from different classes, which have their MRPLs established in USA, EU or China. Sample extracts were further purified using a novel solid-phase extraction (SPE) device, the Oasis PRiME HLB cartridge, which was effective for removal of fats and phospholipids. The method performance was evaluated according to the typical internation criteria for the validation of veterinary drugs. Linearity, precision and recoveries at three concentration levels will be presented.