A sensitive and quantitative liquid chromatography-tandem mass spectrometry method for the simultaneous determination of quinocetone (QTN), a new antimicrobial growth agent, and its two major metabolites de-monoxy-quinocetone (DMO-QTN) and de-dioxy-quinocetone (DDI-QTN) in chicken liver and muscle tissues was developed and validated. Analyte extraction from samples is effectively performed using liquid–liquid extraction by methanol. The assays were based on reversed phase liquid chromatography (LC) coupled with tandem mass spectrometry in the electrospray, positive ion mode using selected reaction monitoring for analyte quantification. Calibration curves showed good linearity for all compounds in the concentration range of 2–500 μg kg−1. The detection limits for measured compounds were all ≤0.003 μg g−1 and quantification limits were all ≤0.010 μg g−1. Intra- and inter-assay CVs were all <10%. The recoveries ranged from 95% to 108%. Finally, the method was applied to real chicken liver and muscle samples, the quinocetone and its two metabolite residues were found only in liver.