| Summary: | Exposomics aims to characterize the totality of exposures over the lifespan, and their impact on human health. Currently, chronic exposure to harmful chemicals from air pollution and/or tobacco smoke, along with a suboptimal diet, remain leading causes for preventable mortality and morbidity worldwide. As a result, new analytical methods are needed to measure robust biomarkers of smoke exposure and food intake for improved risk assessment of clinical events. This thesis aims to develop high throughput methods to rapidly quantify urinary biomarkers of environmental smoke in high-risk occupations, and diverse global populations using multisegment injection-capillary electrophoresis-mass spectrometry (MSI-CE-MS) technology. Chapter II outlines an inter-laboratory method comparison for the targeted analysis of urinary 1-hydroxypyrene (HP) when using gas chromatography-high resolution mass spectrometry (GC-HRMS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) on urine samples collected from firefighters. This work revealed the critical role of incomplete enzymatic deconjugation on method bias and underreporting of true smoke exposures. Chapter III introduces a high throughput MSI-CE-MS/MS method (< 3 min/sample) to directly analyze the intact glucuronide conjugate of HP (HP-G) in urine without complex pre-column enzyme deconjugation and derivatization procedures. Importantly, firefighters deployed under emergency conditions at the 2016 Fort McMurray wildfire had creatinine normalized HP-G concentrations below the biological exposure index, likely caused by delays in urine collection under emergency conditions, at early stages of firefighting. Chapter IV extends from targeted biomonitoring of occupational smoke exposure, towards elucidating the relative risk of tobacco smoking in an international cohort of participants (n=1000) from the Prospective Urban and Rural Epidemiological (PURE) study. Comprehensive analysis of nicotine metabolites in urine by MSI-CE-MS allowed for reliable determination of ...
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