A magnetic macroporous material（Fe,3,O,4,@SiO,2,@PLS） and a metal organic framework composite（Fe,3,O,4,@ZIF－8） were synthesized in this paper，and they both were combined to use as a mixed magnetic adsorbent．Based on this，a high performance liquid chromatography－tandem mass spectrometry‍（HPLC－MS/MS） with the mixed magnetic adsorbent solid phase extraction（MSPE） was established for the quantitative analysis of 4 sulfonamides and 8 quinolones in water samples．The morphologies，chemical structure information and crystalline structures of the prepared materials were characterized by scanning electron microscopy（SEM），Fourier－transform infrared spectroscopy（FT－IR） and X-ray diffractometry（XRD）．The results showed that the prepared Fe,3,O,4,@SiO,2,@PLS appeared nearly spherical in shape，with a large specific surface and an average size of 500－600 nm，nearly without Fe,3,O,4, on the surface，suggesting the formation of core－shell structure Fe,3,O,4,@SiO,2,@PLS，while Fe,3,O,4,@ZIF－8 was nearly spherical in shape，with an average diameter about 200 nm and a rough surface．The crystalline structures of Fe,3,O,4, and ZIF－8 in Fe,3,O,4,@ZIF－8 did not change after the preparation reaction，indicating that the spherical Fe,3,O,4, particles were unifomly attached to the surfaces of the orthohexagnal ZIF－8 crystals．And then the two magnetic nanoparticles were simultaneously introduced to extract 12 antibiotics residues in water samples by MSPE followed by HPLC－MS/MS．In order to establish the optimal extraction conditions，the key parameters influencing MSPE，i.e．magnetic adsorbent amount，adsorption mode，adsorption time，sample pH，elution solvent and elution time were investigated in detail．All the experiments were performed in parallel for three times．In the adsorption procedure of MSPE，12 antibiotics could be extracted completely by the mixture use of 35 mg Fe,3,O,4,@SiO,2,@PLS and 15 mg Fe,3,O,4,@ZIF－8 within 10 min．Elution was performed using 10 mL 5% ammonia methanol for 5 min．The target compounds were separated on an Agilent ZORBAX Eclipse Plus C,18, column（100 mm × 3.0 mm，1.8 μm） by gradient elution，analysed in multiple reaction monitoring（MRM） mode using positive electrospray ionization（ESI,+,）．Under the optimized conditions，good linearities were obtained for 12 antibiotics in the range of 0.5－10 μg/L，with correlation coefficients（,r,2,） of 0.996 1－0.999 8. The limits of detection（LOD，,S/N ,= 3） and the limits of quantitation（LOQ，,S/N ,= 10） were in the ranges of 0.01－0.14 μg/L，0.04－0.45 μg/L，respectively．The recoveries for 12 antibiotics at three spiked levels ranged from 75.0% to 107%，with relative standard deviations（RSD） of 0.50%－5.5%．The proposed method is suitable for the simultaneous determination of trace sulfonamides and quinolones antibiotic residues in water samples．