Trapped Ion Mobility Improves Annotation Accuracy in LC-HRMS Screening Applications for Exposomics

Area of Science:

• Analytical Chemistry
• Environmental Science
• Biomolecular Analysis

Background:

• Liquid chromatography-mass spectrometry (LC-MS) is crucial for analyzing complex samples.
• Coeluting matrix interferences and isomers often complicate LC-MS analysis.
• Collision cross section (CCS) offers a robust, matrix-independent parameter complementary to retention time (RT).

Purpose of the Study:

• To evaluate the advantages of trapped ion mobility spectrometry (TIMS) for analyzing diverse human and environmental matrices.
• To assess TIMS's capability in resolving coeluting compounds and reducing analytical interferences.
• To demonstrate the utility of TIMS in suspect screening applications.

Main Methods:

• Coupling TIMS with mass spectrometry for analyte separation.
• Development of a screening library for 769 environmental contaminants.
• Analysis of human samples (urine, serum, breastmilk) and exposure-relevant matrices (dust, wastewater).
• Comparison of mobility values against reference standards across different ionization modes.

Main Results:

• A library of 948 CCS values (594 positive, 354 negative ionization modes) was generated.
• 112 peaks with distinct mobility values were identified across all matrices, indicating coelution.
• TIMS effectively separated compounds with similar m/z and RT but different mobilograms.
• Significant reduction in inconclusive assignments and improved MS2 coverage for low-abundant ions were observed.

Conclusions:

• TIMS significantly enhances the specificity and reliability of mass spectrometry-based screening.
• The matrix-independent CCS parameter provided by TIMS aids in resolving complex mixtures.
• TIMS is particularly beneficial for suspect screening, improving data quality and reducing false positives.