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An UPLC-MS/MS method based on matrix solid-phase dispersion (MSPD) was developed for simultaneous determination of 15 beta-lactams in pork muscle. Muscle tissue was blended with Oasis HLB adsorbent. A column made from the sorbent/muscle tissue matrix was washed with hexane, after which beta-lactams was eluted with acetonitrile/water (50:50, v/v) both containing 0.1% formic acid. The final extract was evaporated, and reconstituted into acetonitrile/water (10:90, v/v) for the analysis of UPLC-MS/MS. The correlation coefficient (r(2)) with each matrix-matched calibration curve is higher than 0.99. Limits of detection (LODs) and limits of quantification (LOQ5) of beta-lactams were ranged from 0.02 to 0.63 mu g kg(-1) and 0.07-0.97 pg kg(-1), respectively. At the fortified levels, mean recoveries of all compounds were ranged from 92 to 111%, and the RSDs were lower than 12%. The method was accurate and reproducible, being successfully applied to the monitoring of 15 beta-lactams in pork muscles obtained from the Chinese market. (C) 2016 Elsevier Ltd. All rights reserved.