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Not all residues of drugs found in influent wastewater are the result of consumption. Identifying intentional or accidental disposal is crucial in wastewater-based epidemiology to ensure the accuracy of observed spatiotemporal trends in consumption patterns. So far, only a limited number of studies provided analytical evidence for the direct disposal of illicit drugs or pharmaceuticals. Additionally, only minimal standardization in the workflow is employed to distinguish direct disposal from consumption. PubMed, SCOPUS, and Web of Science databases were searched using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA, 2020) guidelines. The search focused on wastewaterbased epidemiology publications in which the dumping event was strongly suspected or identified through (i) parent compound-metabolite ratios, (ii) enantiomeric profiling, and (iii) nontarget and suspect screening. In total, 29 studies were included in this systematic literature review. This study aims to review existing approaches to assess direct disposal of drugs in influent wastewater, review literature for potential dumping events, and proposes a simple evidence-based scoring system for the identification of direct disposal of drugs in influent wastewater, based on available analytical evidence. This framework is a first effort to standardize dumping/disposal assessment, while more research is needed to further refine the decision criteria and analytical techniques used within the proposed strategy.

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Wastewater-based epidemiology (WBE) is based on the analysis of human metabolic excretion products (biomarkers) of xenobiotics in wastewater, to gain information about various lifestyles and health aspects of a population in an evidence-based manner. Due to the complex wastewater matrix and trace level occurrence of human biomarkers in the sewage network, it is crucial to have sensitive analytical procedures available. Additionally, to improve the value of WBE as a complementary epidemiological source, there is increasing pressure on the analysis of more compounds, more locations and more samples. A high-throughput method based on 96-well Oasis MCX solid-phase extraction (SPE), requiring less influent wastewater (2 mL), was developed in accordance with the European Medicines Agency guidelines. Validation was successful for 28 parent drugs and metabolites of antidepressants, opioids and drugs of abuse. The selection of biomarkers and quantification limit was chosen to be relevant for WBE and was predominantly 10 ng/L or below. The final method was successfully applied to 24-h composite samples of October 2019 (n = 27), obtained from an urban wastewater treatment plant in Leuven (Belgium).