Development and Application of an LC-MS/MS Untargeted Exposomics Method with a Separated Pooled Quality Control...

Area of Science:

• Environmental Health
• Analytical Chemistry
• Metabolomics

Background:

• Untargeted methods in exposomics rely on pooled quality controls (QCs) to ensure data quality.
• Traditional pooled QCs can dilute low-level compounds in exposed groups, leading to their omission in analysis.
• This limitation hinders comprehensive human biomonitoring, especially in studies comparing exposed and non-exposed populations.

Purpose of the Study:

• To develop and validate an untargeted analytical workflow for human biomonitoring in urine samples.
• To implement a novel approach for preparing separated pooled quality controls (QCs).
• To enhance the identification of biologically significant compounds in exposomics studies.

Main Methods:

• An untargeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) workflow was established.
• Three distinct pooled QCs were prepared: total samples (QC-T), non-smokers only (QC-NS), and smokers only (QC-S).
• Feature tables were filtered separately using QC-T and a merged list from QC-NS and QC-S (SNS-feature list).

Main Results:

• The separated pooled QC strategy (SNS-feature list) identified a greater number of features compared to the traditional pooled QC (T-feature list).
• This resulted in the identification of a higher number of biologically significant compounds.
• The novel QC approach demonstrated improved sensitivity for detecting compounds in specific exposure groups.

Conclusions:

• The separated pooled quality control strategy effectively addresses the limitations of traditional methods in exposomics.
• This approach significantly improves the comprehensiveness of untargeted human biomonitoring for exposed and non-exposed subjects.
• The developed workflow enhances the discovery of relevant biomarkers in environmental health studies.