Quantification Of Temporal Fractions Of The Human Exposome Using Differential Stable Isotope Coding Technique Coupled With High Resolution Mass Spectrometry

Parinya PANUWET, International Agency for Resaerch on Cancer, France

1 Biomarkers Group, Nutrition and Metabolism Section, International Agency for Research on Cancer, Lyon, France
2 Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada

The exposome conceptually represents the totality of individual’ environmental exposures and how these exposures relate to biological responses leading to disease development. An individual’s exposome is highly variable and dynamic throughout the lifetime; thus its measurement is challenging. Luckily, owing to advanced technologies available to date, the ability to accurately measure different (temporal) fractions of the human exposome has begun to develop. Here, we describe a metabolomic approach developed for the semi-quantification of fractions of the exposome containing a large suite of biomarkers of exposure to dietary and environmental chemicals such as phenols, polyclyclic aromatic hydrocarbons, pesticides, parabens, and phthalates. We employed differential stable isotope coding technique, based on the use of 13C/12C-dansyl chloride and 13C/12C p-dimethylaminophenacyl reagents, to permit compounds containing phenol and amine, or carboxylic acid groups to be uniformly detected using ultra-high resolution mass spectrometry (Hybrid Quadrupole Orbitrap Mass Spectrometer and Quadrupole Time-of-Flight Mass Spectrometer). This approach combines a highly sensitive broad scan detection of hundreds of compounds with the reliable estimation of their presence in biospecimens. In addition, stable isotope coding significantly reduces intrinsic matrix effects, and generally improves sensitivity of the measurements. Exploratory analysis of pooled urine samples revealed detection of 3,5,6-trichloro-2-pyridinol (a metabolite of chlorpyrifos and chlorpyrifos-methyl), bisphenol a, naphthols, and dietary phenols commonly found in trace amounts in urine of different populations. This could, therefore, warrant further use of this approach in large prospective epidemiological studies linking human exposures to cancer risk.