Abstract: A method was developed for the simultaneous determination of 13 quinolone(QNs) antibiobtics in swine muscle by ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). The analytes were extracted from the sample using Na₂EDTA-Mcllvaine buffer solution and phosphate buffer with ultrasonic bath and purified by solid-phase extraction (SPE) cartridge. Sample was analyzed in electrospray positive ion and multiple reaction monitoring(MRM) mode. Satisfied recoveries (64.55%—117.62%) of all the drugs are demonstrated in 5.0，50.0 and 100.0 μg/kg spiked levels with the RSD for intra-day and inter-day of 13 analytes less than 14.28% and 12.81%. Limit of detection (LOD) and limit of quantitation (LOQ) are 1.0 μg/kg and 5.0 μg/kg. The method is simple, accurate, sensitive and suitable for the determination of 13 quinolone(QNs) antibiobtics in swine muscle.