Comparing Suspect and Nontargeted Screening Workflows for Perinatal Chemical Exposome Analysis: A European Interlaboratory Study from the PARC-EU Project

Abstract

Early-life chemical exposures may contribute to adverse health outcomes later in life. However, conventional chemical analyses typically cover only a limited subset of the chemical exposureome. Suspect and nontargeted screening (SS/NTS) using high-resolution mass spectrometry (HRMS) workflows provides a powerful framework for comprehensive assessments of exposure, with the potential to detect a broad range of environmental contaminants and emerging chemicals. An interlaboratory assay involving 12 laboratories was performed to evaluate the comparability and complementarity of SS/NTS approaches for maternal urine, serum, and milk, based on reversed-phase (RPLC), hydrophilic interaction liquid chromatography (HILIC), and gas chromatography (GC) with HRMS. Participants used in-house methods to possibly detect a predefined and shared list of 50 compounds with varying polarities spiked at three concentrations. The overall detection rates ranged from 4% to 72% for all three techniques, with RPLC-HRMS covering compounds with log P 0–6, while HILIC-HRMS and GC-HRMS extended this coverage. Univariate and multivariable analyses of RPLC-HRMS results for serum and urine identified sample preparation steps as key factors influencing detection rates. Workflow performances were additionally benchmarked by using the S-score. These findings demonstrate the complementarity of SS/NTS platforms for extending chemical-space coverage for the most comprehensive exposure characterization. Therefore, efforts should be made for harmonized QA/QC provisions while conserving the added value of different workflows for exposure data for risk assessments.