A method was developed for the determination of amantadine hydrochloride，rimantadine hydrochloride，dexamethasone，tilmicosin and olaquindox metabolite residues in poultry tissues by high performance liquid chromatography coupled with tandem mass spectrometry.The samples were extracted with acetonitrile after hydrolyzed with 2 mol/L sodium hydroxide and adjusted to pH value with hydrochloric acid.The extract was purified with a C18 solid phase extraction(SPE) cartridge，and eluted with methanol(containing 0.1% formic acid) and ammonia methanol(containing 0.1% ammonia).The target compounds were separated with a Phenomenex Kinetex C18(100 mm×4.6 mm，2.6 μm) by gradient elution using 0.1% formic acid containing 5 mmol/L ammonium acetate-methanol as mobile phase，and detected by liquid chromatography-tandem mass spectrometry in ESI under positive ion mode.The calibration curves were linear in the range of 2-100 μg/L for five drugs，with correlation coefficients of 0.996 2-0.999 8.The spiked recoveries of five drugs in poultry tissues at spiked levels of 5-50 μg/kg were in the range of 73.7%-92.3% with relative standard deviations(RSD,n=5) of 3.9%-16.6%.The detection limits(S/N≥3) for five drugs were in the range of 0.2-3.0 μg/kg and the quantitation limits(S/N≥10)were 0.7-10 μg/kg，respectively.The method is rapid，simple，economical and practical，and conforms to regulations requirement.Therefore，the method could meet the demand for routine analysis.