A confirmative method was developed for the simultaneous determination of 46 antibiotics,including sulfonamides，quinolones and macrolides in organic fertilizer by ultrahigh performance liquid chromatography-tandem massspectrometry(UPLC-MS/MS).The samples were extracted with acetonitrile-EDTA buffer solution(pH 10.0),and separated by centrifugation after salting out.The upper acetonitrile layer was purified by the QuEChERS steps with sorbents.The buffer solution layer was purified with solid-phase extraction cartridge.The separation of target drugs was performed on an ACQUITY UPLC BEH C18column using a mobile phase consisting of 2 mmol/L ammonium acetate with 0.1% formic acid and methanol by gradient elution．The analysis of target compounds was carried out with positive electrospray ionization(ESI+)source under multiple reaction monitoring(MRM) mode.The matrix-matched external standard calibration was used for quantification.Good linearities for the 46 antibiotics were achieved over the concentration of 1-200 μg/L,with correlation coefficients(r2) of 0.996 6-0.999 9.The recoveries of sulfonamides,quinolones and macrolides at spiked levels of 25，100,400 μg/kg were in the range of 67.8%-95.6%,65.6%-89.4% and 66.6%-107.8%,respectively,with relative standard deviations(RSDs) of 0.4%-11.9%.The limits of detection(LOD,S/N=3) were 0.6-4.6 μg/kg,and the limits of quantitation(LOQ,S/N=10) were 2.1-15.4 μg/kg.