Nabumetone is one of the non-steroidal anti-inflammatory drugs, characterized by its non-acidic and lipophilic properties. Its pharmacological effects are achieved through the metabolite 6-methoxy-2-naphthylacetic acid, which is an inhibitor of the cyclooxygenase enzyme. Interaction of ionizing radiation and the substance results in the formation of reactive short- lived particles, oxidizing and reducing species, which, through non-selective reactions, react with pharmaceuticals and can transform them into environmentally benign products. In this work, high performance liquid chromatography and UV/Vis spectrophotometry were used for the quantification of nabumetone. The degradation efficiency was monitored in aqueous solutions at different initial concentrations of nabumetone, different radiation doses, and different pH values. Additionally, the impact of various radical scavengers, inorganic ions, and solvents was observed. A coupled system of ultra-high-performance liquid chromatography and high-resolution mass spectrometry was used for the analysis of nabumetone degradation products. Based on the results of tandem mass spectrometry analysis, structures and fragmentation schemes of nabumetone degradants were proposed.