A robust multiwell workflow for quantitative and nontargeted chemical exposomics at cohort scale
Abstract
Chemical exposomics enables comprehensive profiling of environmental substances and their metabolic perturbations, providing new opportunities to uncover environmental drivers of disease. To realize its full potential in human exposome initiatives, more reproducible high-throughput workflows are needed that combine sensitive quantitative targeted analysis with nontargeted molecular discovery in small serum volumes. We describe a 96-well phospholipid depletion workflow using 100 µL of serum and liquid chromatography – high-resolution mass spectrometry to quantify 247 priority pollutants, drugs and metabolites while confidently annotating hundreds of additional exogenous and endogenous molecules. In contrast to evaporation-to-dryness workflows, adding a small volume of dimethyl sulfoxide retained more analytes and improved recovery (99% median target recovery), with negligible effect on sensitivity (0.5 ng/mL median method limit of quantification), resulting in robust within-laboratory reproducibility across four operators over 1.5 years (18% median relative standard deviation). Application to 718 human serum samples confirmed scalability while maintaining reproducible quantitation and molecular discovery (761 annotated substances) at the cohort scale.
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BibTeX
@misc{thiele2026robust,
title = {{A robust multiwell workflow for quantitative and nontargeted chemical exposomics at cohort scale}},
author = {Solveig Thiele and Bénilde Bonnefille and Sophia Harlid and Stefano Papazian and Jonathan W. Martin},
howpublished = {ChemRxiv},
year = {2026},
month = oct,
doi = {10.26434/chemrxiv.15009862/v1},
url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009862/v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - A robust multiwell workflow for quantitative and nontargeted chemical exposomics at cohort scale
AU - Solveig Thiele
AU - Bénilde Bonnefille
AU - Sophia Harlid
AU - Stefano Papazian
AU - Jonathan W. Martin
PY - 2026
DA - 2026/10/05
PB - ChemRxiv
DO - 10.26434/chemrxiv.15009862/v1
UR - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009862/v1
AB - Chemical exposomics enables comprehensive profiling of environmental substances and their metabolic perturbations, providing new opportunities to uncover environmental drivers of disease. To realize its full potential in human exposome initiatives, more reproducible high-throughput workflows are needed that combine sensitive quantitative targeted analysis with nontargeted molecular discovery in small serum volumes. We describe a 96-well phospholipid depletion workflow using 100 µL of serum and liquid chromatography – high-resolution mass spectrometry to quantify 247 priority pollutants, drugs and metabolites while confidently annotating hundreds of additional exogenous and endogenous molecules. In contrast to evaporation-to-dryness workflows, adding a small volume of dimethyl sulfoxide retained more analytes and improved recovery (99% median target recovery), with negligible effect on sensitivity (0.5 ng/mL median method limit of quantification), resulting in robust within-laboratory reproducibility across four operators over 1.5 years (18% median relative standard deviation). Application to 718 human serum samples confirmed scalability while maintaining reproducible quantitation and molecular discovery (761 annotated substances) at the cohort scale.
ER -