Presence and Fate of Carbamazepine, Oxcarbazepine, and Seven of Their Metabolites at Wastewater Treatment Plants

Many pharmaceuticals are excreted in wastewater as parent substances or metabolites subsequent to therapeutic or diagnostic application in medical care. This includes the antiepileptic carbamazepine, which is not removed during conventional wastewater treatment and was found to be ubiquitous in the aquatic environment. Some carbamazepine metabolites have also been found in treated wastewater, but only five of them have been studied to date. However, at least 30 carbamazepine metabolites have been identified in humans, including some pharmacologically active or genotoxic compounds. Oxcarbazepine, an antiepileptic which is increasingly used, generates metabolites common to those of carbamazepine. The present work focuses on the presence of carbamazepine, oxcarbazepine, and seven of their metabolites (carbamazepine-10,11-epoxide, 10-hydroxy-10,11-dihydrocarbamazepine, 10,11-dihydro-10,11-trans-dihydroxycarbamazepine, 2-hydroxy-carbamazepine, iminostilbene, acridine, and acridone) at three different treatment plants (conventional activated sludge, trickling filter, and stabilization ponds) selected in France. The main aim of this work was to identify selected compounds in wastewater after therapeutic use and to measure concentrations in influents and effluents at the three wastewater treatment plants. Except for iminostilbene, all of these compounds were detected in wastewater. The metabolite common to carbamazepine and oxcarbazepine, i.e., 10,11-dihydro-10,11-trans-dihydroxycarbamazepine, was detected at a higher concentration than the parent substances in wastewater. The presence of parent molecules was noted in inlet and outlet water samples. Carbamazepine, as expected, was not removed by conventional activated sludge treatment. Nevertheless, in a wastewater treatment plant with a 78-day hydraulic retention time, a 73% decrease in carbamazepine concentration was observed. For the first time, oxcarbazepine was found in environmental samples. A decrease in oxcarbazepine concentrations was observed at the three sewage treatment plants, with removal ranging from 24 to 73%. No metabolite removal was observed after activated sludge treatment. In the two other sewage treatments plants, the fate of the metabolites differed. The concentration of some metabolites, e.g., 10,11-dihydro-10,11-trans-dihydroxycarbamazepine and acridine, increased, possibly via different processes such as cleavage of glucuronide conjugates or biotic and abiotic degradation of parent compounds. The behavior of the studied substances is discussed in terms of the treatment process and hydraulic retention time.