Based on solid phase extraction (SPE) with Fe3O4 magnetic nanocomposite @ graphene (MNP@G) as adsorbent, an approach was developed for determination 15 quinolone antibiotics in water by high performance liquid chromatography and tandem mass spectrometry (HPLC–MS). The main factors affecting the extraction efficiency were investigated. The optimized extraction conditions were: 10% ammonia in methanol (V/V) as elution solution, 30 mg MNP@G as adsorbent, 30 min adsorption time. Under the conditions, the detection limit of 15 quinolone antibiotics were from 6.5 to 12.8 ng/L, the calibration curves showed good linearity (r =0.999 1～0.999 8) with the concentration range from 10 to 500 ng/L. The developed approach was perfectly applied in the analysis of tap water, agricultural and medical wastewater. The recoveries ranged from 70.0% to 90.7% for the 3 real spiked samples, and the relative standard deviations were all less than 10%.