Mood Altering Waters: Multidimensional Profiling and Chiral Characterization of Antidepressants in Effluent-Impacted Waterways

Antidepressants (ADs) and their metabolites are widely reported in wastewater effluent and effluent-impacted waterways due to incomplete removal during wastewater treatment. These chemicals have been known to influence the behavior and physiology of exposed organisms, raising concerns regarding the ecological impact of this contamination. However, although 28 ADs are approved by the United States Food and Drug Administration, environmental studies commonly target only a small fraction of these chemicals, as conventional analytical approaches are hindered by coeluting isomers and structural similarity. Here, we developed a multidimensional workflow integrating liquid chromatography, drift tube ion mobility spectrometry, mass spectrometry, and fragmentation analysis to enable high-confidence identification and targeted quantification of 26 parent and 8 AD metabolites in environmental samples, while also establishing a publicly available reference library to support future studies. Selected compounds were further characterized with chiral chromatography to assess enantiomeric ADs with differing biological activity. This workflow was applied to effluent-impacted waterways, enabling the identification and quantification of 17 AD chemicals across five sites. These findings highlight the prevalence of AD contamination and the need for improved monitoring and wastewater treatment strategies to mitigate ecological and human health risks.