Quantitative Exposomics Targeting over 200 Toxicants and Key Biomarkers at the Picomolar Level

Area of Science:

• Environmental Health Sciences
• Analytical Chemistry
• Toxicology

Background:

• The exposome, encompassing all environmental exposures, is crucial for understanding health and disease.
• Current methods for analyzing trace-level exposure chemicals often lack sensitivity and broad applicability for large studies.
• Large-scale exposome-wide association studies (ExWAS) require robust, high-throughput analytical workflows.

Purpose of the Study:

• To develop and validate a scalable, next-generation human biomonitoring (HBM) workflow for comprehensive exposomic analysis.
• To establish validation criteria for high-throughput assays analyzing diverse trace-level compounds.
• To demonstrate the workflow's utility in a real-world epidemiological setting.

Main Methods:

• A solid-phase extraction method using 96-well plates coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS).
• Analysis of over 230 biomarkers in urine, plasma, and serum.
• Validation of method robustness, including extraction recovery, matrix effects, precision, and sensitivity (limit of detection <0.1 ng/mL).

Main Results:

• The workflow demonstrated robust performance across biological matrices, with 59-80% of analytes meeting validation criteria.
• Over 100 analytes, including PFAS, pesticides, and industrial chemicals, were detected in 200 urine samples from pregnant women.
• Several analytes were detected for the first time in a U.S. urinary biomonitoring study.

Conclusions:

• The developed HBM workflow is scalable, sensitive, and robust, suitable for large-scale exposomic research.
• This method supports the advancement of exposome-wide association studies (ExWAS) for public and personalized prevention.
• The proposed validation framework aids in assessing assays for complex, trace-level chemical analyses.