The combined extracts were reduced to dryness under nitrogen flow in a water bath heated to 40°C. The samples were re-suspended in 2ml acetonitrile/water (10:90) by sonication for 5 min. Remaining particles were removed by passing the extracts through a 0.7 um glass-fiber filter (Sartorius, Brussels, BE) into 2mL amber glass LC-MS vials. LC-HRMS Analysis. LC-HRMS analysis was performed on a Thermo QExactive HF Mass Spectrometer equipped with a Waters Acquity UPLC BEH C18 column (1.7μm, 2.1x150mm) using both positive and negative electrospray ionization with the following spray settings (positive/negative): sheath gas flow rate (45/60 arbitrary units, AU), auxiliary gas flow rate (10/25 AU), sweep gas flow rate (2/2 AU), spray voltage (3.5/3.6 kV), capillary temperature (320/300 °C), S lens RF (50/50 AU), and auxiliary gas temperature (300/370 °C). Mobile phase A (water with 0.1% formic acid) and B (methanol) were mixed using the following LC gradient starting at 90A/10B at 0 min, 90/10 at 2 min, 0/100 at 15 min, 0/100 at 20 min, 90/10 at 21 min, and ending with 90/10 at 30 min at a flow rate of 0.200 mL/min. The following data-dependent (dd-)MS2 settings (in display order of instrumental acquisition method) were used: resolution (120,000 at m/z 200), automatic gain control (AGC) target (1.0×10 ), maximum injection time (IT): (70 ms), and scan range (m/z=60-900). For the selected ion monitoring dd-MS2/ddSIM the following were used: resolution (30,000 at m/z 200), AGC target (5.0×10 ), maximum IT (70 ms), loop count (5), Top N (5), isolation window (1.0 Da), (N)CE (30). Lastly, the following dd settings were used: minimum AGC target (8.0×10 3 ), intensity threshold (1.1×10 5 ), apex trigger (4-6 s), exclude isotopes (On), and dynamic exclusion (10.0 s). The instrument was calibrated and optimized every time an analysis was performed using manufacturer settings to ensure consistent performance throughout the 2-year study. Suspect Screening. Suspect screening was performed using two suspect lists. The first list contains 816 unique pharmaceutical compounds (Supporting Information, Table CNS 'Caisse Nationale de Santé' Suspects, also available on the NORMAN Suspect List Exchange, NORMAN-SLE) that were curated from the Luxembourgish National Health Fund's "List of marketed medications in Luxembourg". These drugs have marketing authorisation in Luxembourg from the Ministry of Health and are therefore potentially in use domestically. For suspect screening, MS-Ready SMILES of these compounds were obtained via the EPA CompTox Chemistry Dashboard's batch search function. Using MS-ready SMILES as a structural identifier ensures that the structure being used for data analysis is consistent with what is measured by the mass spectrometer, and at the same time remains traceable within online chemical databases. The second suspect list consists of 82 pharmaceutical TPs. These TPs were derived from two sources: PubChem , and a recent study by Anliker et al. . From PubChem, TPs were obtained from the Transformations table of a given compound (where available) using R scripts written to programmatically download transformation product information . The TP information in PubChem originates from the NORMAN Suspect List Exchange. Sixty-seven TPs were extracted from PubChem in this way (coming from a total of 53 parents -44 parents were on the original CNS list of 816 parent compounds, while the remaining 9 parents are actually themselves TPs with reciprocal transformations). The remaining 15 TPs were obtained from Anliker et al. . Curation of the final suspect list involved deduplication and multiple steps of interconversion between chemical identifiers (e.g., CAS to PubChem CID, InChIKey to CID) using PubChem's Identifier Exchange Service 37 to facilitate compound comparisons and ensure that the final list of 82 TPs was unique. Then, the final SMILES ("parent SMILES" in PubChem terms, "MS-ready" SMILES in CompTox terms) were retrieved. More information and the full R code is available in the SI and on GitLab as a Jupyter Notebook .