High-resolution MS and MSn investigation of ozone oxidation products from phenazone-type pharmaceuticals and metabolites

•Ozone was applied for the oxidation of four phenazone-type compounds.•Seventeen degradation products were determined using HR-MS and MSn experiments.•The second-order rate constants of oxidation were determined by competition kinetics.•The toxicity of the degradation products was assessed using a QSAR model. Phenazone-type pharmaceuticals, such as aminopyrine, metamizole, phenazone and propyphenazone, are widely used analgesics that have been detected in wastewater treatment plant effluents in μgL−1 concentrations. Acetamido antipyrine (AAA) and formyl aminoantipyrine (FAA) – the main metabolites of aminopyrine and metamizole – have also been detected in sub μgL−1 concentrations in environmental water bodies and in resources used to produce drinking water, suggesting their highly persistent character. In this study phenazone, propyphenazone, AAA and FAA were treated with ozone under laboratory conditions and 17 degradation products were identified by an elucidation approach based on high-resolution mass spectrometry (LTQ Orbitrap). Typical oxidation of carbon–carbon double bonds by ozone was observed among other mechanisms of ring opening. It was demonstrated that reactivity of these compounds with ozone is high (rate constants kO3 ranging from 6.5×104 to 2.4×106M−1s−1). The toxicity of the degradation products from ozonation was estimated by quantitative structure–activity relationships (QSAR). It was shown that, when the carbon–carbon double bond is partially oxidized to an epoxy, the toxicity towards fish and daphnids is higher than that of the parent compound. By further oxidizing the molecules, a common degradation product – 1-acetyl-1-methyl-2-phenylhydrazide (AMPH) – was also found to be more toxic than its parent compounds, which is of concern since this compound has previously been reported in environmental waters.