High-Resolution MS and MSn Investigation of UV Oxidation Products of Phenazone-type Pharmaceuticals and Metabolites

Abstract

The occurrence of phenazone-type analgesics, such as aminopyrine, metamizole, phenazone and propyphenazone, has been reported in the effluent of wastewater treatment plants in µg/L concentrations. The presence of the main metabolites of aminopyrine and metamizoleacetamido antipyrine and formyl aminoantipyrinehas even been detected in sub µg/L concentrations in surface water and water bodies used to produce drinking water. This points at their high persistence and the need for adequate removal strategies. The degradation of phenazone, propyphenazone, acetamido antipyrine and formyl aminoantipyrine by UV radiation was investigated under laboratory conditions. An elucidation approach based on high-resolution mass spectrometry resulted in the identification of 11 degradation products. A mechanism of ring opening via the oxidation of the N-N bond of the pyrazolone ring was observed as well as the more typical oxidation of carbon-carbon double bonds. Aside from the degradation products, the capacity of formyl aminoantipyrine to produce trimers and dimers was demonstrated. The dimers were shown to be persistent despite continuous UV radiation. The toxicity of the degradation products was assessed by quantitative structure-activity relationships. It was shown that, when the carbon-carbon double bond is partially oxidized to an epoxy, the toxicity towards fish and daphnids is increased with respect to the parent compound.

Degradation of sulfamethoxazole by heat-activated persulfate oxidation: Elucidation of the degradation mechanism and influence of process parameters

“…To assess the potential acute and chronic toxicity of the identified degradation products, the ECOSAR (ECOlogical Structure-Activity Relationship) predictive model, developed by the US Environmental Protection Agency was used as done in previous literature [19,20]. In terms of acute toxicity, 96-h Half Lethal Concentration (LC 50 ) for fish, 48-h LC 50 for daphnia and 96-h…”

Identification of New Oxidation Products of Bezafibrate for Better Understanding of Its Toxicity Evolution and Oxidation Mechanisms during Ozonation

“…18,20 For phenazonetype pharmaceuticals and metabolites, the toxicity estimation QSAR and EPI Suite software were used to assess the ecotoxic potential of OPs characterized by structure applying high resolution (HR) mass (MS) and multiple tandem mass (MS n ) spectrometry. 19,21 Similarly to other PPCPs, BF was reported to be effectively removed by ozonation. 22−26 However, an increase of acute toxicity during its ozonation was observed.…”