Analytical methods for the determination of antidepressants, antipsychotics, benzodiazepines and their metabolites through wastewater-based epidemiology

The wastewater-based epidemiology approach, popular for estimating illicit drug use, has been used to evaluate lifestyle habits such as alcohol, tobacco and caffeine consumption, health biomarkers including pharmaceuticals, plasticizers and flame retardants, and recently to track SARS-CoV-2 at the population level. Equally, the number of WBE studies investigating psychoactive pharmaceuticals such as antidepressants, antipsychotics and benzodiazepines has also increased, which can be connected to the overall growth of psychological disorders worldwide. This review aims to discuss novelties in sampling techniques and analytical methodologies, including sample preparation and analysis, developed for estimating the consumption of psychoactive pharmaceuticals in defined populations. Seventy-four peer-reviewed studies monitoring psychoactive pharmaceutical consumption published since 2010 have been systematically reviewed. Its findings show that a broad range of bioanalytical methodologies is used to simultaneously measure several antidepressants, antipsychotics, benzodiazepines, and their metabolites from influent wastewater samples in low concentrations and different time periods. The application of WBE commenting on the temporal and spatial variations worldwide, showing widespread consumption, is also discussed. Despite much progress and excellent studies, there remains a need for research, and deeper knowledge is needed to reduce method uncertainty, especially since excretion rates, their transformation, and in-sewer and in-sample stability for many psychoactive pharmaceutical biomarkers are not available.