A differential isotope labelling approach to quantifying a large fraction of the human exposome: A focus on chemicals of high concern

Abstract

Understanding of how multiple exposures interplay with physio-genetic characteristics is important to unveil the impact of the human exposome on disease development. This requires accurate measurements of internal and external exposures. External exposure assessment focuses on measuring environmental stressors that include toxic chemicals or chemicals of high concern. Here, we describe a novel method based on differential 12C-/13C-isotope labeling developed for screening and quantifying a large suite of urinary metabolites of chemicals such as polycyclic aromatic hydrocarbons, organophosphate insecticides, parabens, bisphenol A, chloro- and other phenols, phytoestrogens, phthalates, pyrethroid insecticides, and chlorophenoxy herbicides. This method utilizes enzymatic deconjugation of glucuronides and sulfate esters, solid phase extraction, and chemical derivatization with 13C-/12C-dansyl chloride (phenols and amines) and 13C-/12C-p-dimethylaminophenacyl bromide (carboxylic acids) for uniformed and effective ionization during their quantification using high-resolution mass spectrometry. The method has the detection limits suitable for generating data on the individual and population level exposome by means of analysis of individual and pooled urine samples, respectively. As shown in our primary results, the application of this method should support multiple epidemiological studies aiming to investigate the health effects of combined exposures to multiple chemicals.