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.
Tarek Moufawad, K. Ayeni, E. Baira et al.· Environmental Science &...· 0 citations
Broad coverage exposome- and metabolome-wide association studies rely on advanced instrumentation, typically anchored in liquid chromatography-high-resolution mass spectrometry (LC-HRMS) to investigate exposure-effect associations. Sample preparation for biological fluids is a delicate matter, as it is essential to strike a pragmatic balance between sensitivity, chemical coverage, robustness, and time efficiency to meet the requirements of large-scale epidemiological studies. Here, we established a protein precipitation workflow in a scalable, high-throughput format for human plasma and urine. Different protocols were evaluated utilizing a xenobiotic mixture containing >200 exposure compounds based on extraction recovery, repeatability, and applicability for nontargeted analysis (NTA) and suspect screening. The tested high-throughput options included a protein precipitation workflow in 96-well plates and a phospholipid removal plate. For urine, a dilute-and-shoot approach was additionally tested. The plate-based protein precipitation resulted in superior performance with acceptable extraction recoveries (RE, 60-140%) for >70% of the highly diverse analyte panel in plasma and >80% in urine, and acceptable repeatability with relative standard deviations of <30% for more than 95% of analytes in plasma and 80% in urine. NTA results exhibited only a small number of altered annotated features compared to a tube-based protocol used for benchmarking, while increasing the overall time efficiency by a factor of five. To further test the protocol, it was applied to the NIST plasma standard reference material SRM1950. A total of 22 toxicants were identified and (semi-)quantified, with most concentrations comparable to available reference values. The results demonstrate the suitability of the established protocol for combined MWAS/ExWAS.
Julia Füreder, Amira Müller, Giulia Guerra et al.· Analytical Chemistry· 0 citations
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