Gamma-radiolytic degradation of nabumetone in water

Abstract

Nabumeton je jedan od nesteroidnih lipofilnih protuupalnih lijekova. Farmakološko djelovanje ostvaruje putem metabolita 6-metoksi-2-naftiloctene kiseline, koji je inhibitor enzima ciklooksigenaze. Međudjelovanjem ionizirajućeg zračenja i tvari nastaju reaktivne kratkoživuće čestice, oksidirajuće i reducirajuće vrste, koje neselektivnim reakcijama reagiraju s farmaceuticima te ih mogu prevesti u za okoliš neškodljive produkte. U sklopu ovog diplomskog rada, za kvantitativno određivanje nabumetona korištena je tekućinska kromatografija visoke djelotvornosti i UV/Vis spektrofotometrija. Djelotvornost razgradnje praćena je u vodenim otopinama pri različitim koncentracijama nabumetona, različitim dozama zračenja te različitim vrijednostima pH. Također, praćen je i utjecaj različitih "hvatača" radikala, anorganskih iona te otapala. Spregnuti sustav tekućinske kromatografije ultravisoke djelotvornosti i spektrometrije masa visokog razlučivanja korišten je za analizu razgradnih produkata nabumetona. Na temelju rezultata analize tandemnom spektrometrijom masa, pretpostavljene su strukture i sheme fragmentacije razgradnih produkata nabumetona.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