In order to determine the residue of cyproheptadine hydrochloride（CYP）in swine urine,an internal standard method,namely dispersive liquid-liquid micro extraction/ultra performance liquid chromatography-tandem mass spectrometric（UPLC-MS/MS）method,was established.5 mL swine urine was adjusted to pH 11.0 by 5% aquous ammonia.The sample was extracted with 2 mL chloroform（extractant）-isopropyl alcohol（dispersant）by a ratio of 5∶3.The extractant was separated by 8 000 r/min centrifugation in 4 ℃,and evaporated with nitrogen at 50 ℃.The residue was dissolved with 1 mL 0.1% formic acid∶acenitril（80∶20）and detected by UPLC-MS using diphenylpyraline hydrochloride as an internal standard,with positive electrospray ionization under multi-reaction monitoring mode.The results showed that the linear range of CYP was in the range of 0.5-25 μg/L with a correlation coefficient of 0.999 5.The LOD of the method was 0.05 μg/L,while the LOQ was 0.1 μg/L.The recoveries of cyproheptadine hydrochloride at spiked range of 0.1-5.0 μg/L were in the range of 90.2%-109.7% with RSDs no more than 8.5%.The method showed good accuracy and precision.