Abstract
The environmental occurrence of psychiatric drugs is a growing concern due to their widespread use and persistence in aquatic systems. In this study, haloperidol and aripiprazole, two commonly prescribed antipsychotic agents, were selected as model compounds to investigate their photocatalytic modification and assess the formation of transformation products (TPs). A high-performance liquid chromatography-high-resolution mass spectrometry (HPLC-HRMS) method was developed for the identification and structural elucidation of TPs generated via TiO2-mediated heterogeneous photocatalysis in ultrapure water. Reverse-phase chromatographic separation was achieved using an octadecyl silica column as the stationary phase, with formic acid and acetonitrile as the mobile phase. The total run time of 37 min provided adequate resolution for the separation of the main TPs isomers. TPs annotation was carried out using orbitrap technology, operated at a resolving power of 60 000 for all experiments. Including isomers, a total of 32 haloperidol TPs and 13 aripiprazole TPs were identified, with proposed fragmentation pathways established through targeted MSn experiments. The method was then applied to the analysis of real river surface water samples collected from the Po and Sangone Rivers in Northern Italy over a 3-month period. Following solid-phase extraction (SPE), both parent compounds and TPs were recognized and semi-quantified by retention time, exact mass, and MS2 spectral data. Haloperidol and aripiprazole were detected at maximum concentrations of 27 and 67 ng L-1, respectively. To assess the potential biological impact, in vitro cytotoxicity tests were conducted on normal (BEAS-2B) and oncogenic (BEAS G12C) human bronchioalveolar epithelial cell lines. Although the parent drugs exhibited negligible toxicity at the tested concentrations, haloperidol TPs induced marked cytotoxic effects in both cell models. These results highlight the necessity of including TPs in environmental monitoring and toxicological assessments.
Keywords:
aripiprazole; haloperidol; high‐performance liquid chromatography–high‐resolution mass spectrometry (HPLC–HRMS); river surface water; titanium dioxide; toxicity test; transformation products.