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

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 metamizole—acetamido antipyrine and formyl aminoantipyrine—has 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 daphnid is increased with respect to the parent compound.