Degradation of cimetidine by oxidative processes, mass spectrometry products elucidation and toxicity evaluation

The use of pharmaceuticals has gradually increased and they have become a concern due to the ecological potential impact. Cimetidine (CIM), employed in the treatment of gastrointestinal disorders, is detected frequently in waters worldwide. In this study, CIM aqueous solutions were exposed to four oxidative processes: chlorination (NaClO), ozonation (O3), photocatalysis (UV/TiO2) and photolysis (UV). Low removal of organic matter was observed by total organic carbon measurement. CIM removal was determined by mass spectrometry. CIM was completely degraded in the chlorination and ozonation experiments but not by photodegradation. The results indicate that CIM removal occurs by transformation into persistent degradation products. Seven products, among them five have until now not been reported, were elucidated throughout the experiments by high resolution mass spectrometry and the CIM degradation reaction pathways were proposed. The degradation products were mainly formed by the oxidation of thioether, addition of hydroxyl radicals and oxidative cleavage. No difference in MTT cytotoxicity against HepG2 cells between the treated and untreated CIM solutions was observed. For solutions treated by photolysis, a trend of decreased cell viability with increasing concentration was observed. The ECOSAR software was used to estimate the toxicity of degradation products by structure-activity relationship. Among the identified products only one (CIM-97 - C5H8N2) was considered harmful for the organisms evaluated. The toxicity may be attributed to the presence of the imidazole group, present in molecules of biological importance and used in pharmaceutical industry.