CIL-ExPMRM

CIL-ExPMRM performs exposomic suspect screening by combining chemical isotope labeling and pseudo-multiple reaction monitoring to enhance detection and quantification of polar urinary exposure biomarkers.

Key Features:

• Chemical Isotope Labeling: Uses dansyl chloride (DnsCl) and N-methylphenylethylamine (MPEA) with isotope-labeled counterparts to derivatize polar hydroxyl and carboxyl compounds in urinary biomarkers, increasing detection sensitivity.
• Pseudo-Multiple Reaction Monitoring: Employs pseudo-MRM acquisition to facilitate identification and quantification of exposure chemicals without requiring MS/MS data.
• Automated Optimization and Analysis: Provides scripts to optimize MRM transition parameters, predict retention times (RT), automate dynamic MRMs, and perform peak assignment, alignment, and statistical analysis.
• Extensive MRM Database: Curates an MRM database containing over 70,000 compounds for suspect screening and transition generation.
• Validation and Performance: Reported validation across instrumental platforms with a false positive rate of 10.7%.

Scientific Applications:

• Exposome analysis via urinary biomarkers: Enables comprehensive screening of polar urinary exposure biomarkers for environmental health studies.
• Identification and quantification of low-concentration exposure chemicals: Enhances sensitivity and throughput for chemicals present at low concentrations.
• Retention time prediction and collision energy optimization: Supports improved chemical identification and quantification through RT prediction and collision energy optimization.
• Exposure–disease association studies: Facilitates quantification of exposure biomarkers to support studies linking environmental exposures to disease.

Methodology:

Chemical isotope labeling with DnsCl and MPEA and their isotope-labeled counterparts, pseudo-MRM acquisition, scripts to optimize MRM transition parameters, predict retention times (RT), automate dynamic MRMs, and perform peak assignment, alignment, statistical analysis, and curation of an MRM database of over 70,000 compounds.