Extending the chemical space in human urine by target and suspect screening of persistent and mobile organic compounds

Human exposure to persistent and mobile organic compounds (PMOCs) remains understudied due to analytical challenges. This study analysed 150 urine samples from a university community using a "dilute-and-shoot" approach followed by mixed-mode liquid chromatography-high-resolution mass spectrometry. Target analysis revealed 7 PMOCs with quantification frequencies above 70 %, including sweeteners aspartame (99 %) and saccharin (85 %), while cyclamate exhibited the highest concentrations (GM: 1782 ng/mL) despite lower detection frequency (21 %). Risk assessment indicated no health concerns for sweeteners; however, 17 % of participants showed potential risks from N-desmethyl-acetamiprid, a neonicotinoid metabolite. Among industrial chemicals, toluene-4-sulfonamide was highly prevalent (>90 %) and showed indications of potential risk in 24 % of cases, though this compound was only semi-validated. Multiple linear regression (MLR) confirmed univariate findings, such as elevated aspartame levels in students, and additionally uncovered additional associations. Notably, alcohol consumption, caffeine intake, and personal care product use were positively linked to increased industrial PMOC concentrations, highlighting complex exposure determinants shaped by lifestyle factors. Suspect screening annotated 60 additional compounds, predominantly industrial chemicals, including intermediates and fragrance components, and 7 were confirmed by analytical standards. Caffeine was detected in 79 % of samples, with older participants exhibiting higher exposure, while younger participants showed elevated levels of some fragrances. Moreover, negative associations of caffeine with smoking and plastic use, and positive associations of aniline with caffeine intake were elucidated. Overall, the integration of targeted and non-targeted screening with MLR modelling elucidated intricate exposure patterns influenced by demographic and behavioural factors, significantly advancing the characterization of the polar spectrum of the human exposome.