). In terms of pharmaceutical class, many of the compounds identified in this work belong to drugs for the management of heart related diseases (15), psychoactive drugs (15), antimicrobials (8), and drugs for the management of pain (8). All 5 chemicals monitored by AGE were also detected in this study. Flucytosine on its own is used as an antifungal agent, while morphine can be used as the parent compound for pain management. In addition, two TPs (2-hydroxycarbamazepine and 10,11-dihydroxycarbamazepine) were tentatively identified (Level 3) during the parent pharmaceutical screening because they were isobaric with some parent pharmaceuticals. Eisch-Mersch (2019, location 7 in Figure ), SÛRE -amont Erpeldange (2020, location 3, Figure ), and Our amont Wallendorf Pont (2020, location 10, Figure ). The stimulant caffeine, antidepressant metabolite O-desmethylvenlafaxine, antihypertensive drugs irbesartan and telmisartan, the anti-diabetic drug sitagliptin, and the opioid analgesic tramadol were among the most concentrated pharmaceuticals found in Luxembourgish surface waters (Figure and 3) in both 2019 and 2020. From a temporal point of view (Figure ), the highest median concentrations of the pharmaceuticals were detected in September and October of 2019, and are consistently lower during the spring. The most visually obvious differences between the two sampling years include: 1) amytriptyline, iohexol, phenylalanine, and ranitidine were only detected at quantifiable levels in 2019 and 2) decreases in the median concentrations of dexpanthenol, metformin, nicotine, sotalol, and vildagliptin. As an example, metformin had median concentrations of 3.0 ng/L (May) to 39 ng/L (October) in 2019, much higher than the highest detected median concentration of metformin in 2020 (0.62 ng/L in August 2020). Dexpanthenol is a drug used for prophylactic purposes, both metformin and vildagliptin are drugs used for managing diabetes, sotalol is for the management of arrhythmia, while nicotine relates to smoking. A juxtaposition of data from 2019 and 2020 are presented as boxplots in Figure , showing the general decrease in many pharmaceutical concentrations in 2020 (green boxes). For simplicity, only the top 50 pharmaceuticals ranked by median concentration are presented. Some of the most notable drops in detected concentration was observed for dexpanthenol, nicotine, metformin, and sotalol. Factors that affected pharmaceutical concentrations in Luxembourg. Interestingly, lower median concentrations of the pharmaceuticals were measured in 2020 compared to 2019 (as shown in Figure ), which may be partially due to the reduced presence of cross-border workers during the pandemic. COVID-19 has brought on a major shift in working practices, as more people were advised and allowed to work remotely. In Luxembourg, a major part of the workforce is comprised of cross-border workers (approximately 206,000 people in 2019). This translates to an approximately 25% decrease in the daytime population, which may translate to reduced pharmaceutical loading in the sewage system. Two interesting features in Figure , also apparent in Figure , are the detections of iohexol and ranitidine in 2019 but not in 2020. Iohexol is a radiocontrast agent used for medical imaging. Due to the COVID-19 pandemic, there was a significant decrease in medical procedures for non-communicable diseases, including radio imaging. This decrease may explain why iohexol was not detected at a quantifiable level in 2020 despite having the 6 th highest median concentration in 2019. Ranitidine use in the EU, on the other hand, was discontinued in 2020 because of the suspected carcinogen N-nitrosodimethylamine, an impurity present in ranitidine drugs. It is interesting to see how changes in drug usage are abruptly reflected in their detection in the environment.