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

Ion mobility techniques coupled to mass spectrometry, such as trapped ion mobility (TIMS), are promoted to separate analytes from coeluting matrix interferences and to resolve isomers based on their corresponding CCS values. Complementary to the retention time (RT) dimension revealed from liquid chromatography, the collision cross section (CCS) serves as a robust and matrix-independent parameter. We evaluated the advantages of TIMS in the screening of human samples, such as urine, serum, breastmilk, and matrices relevant for exposure analysis, such as dust and wastewater. We conducted a screening library for 769 environmental contaminants, which resulted in a total of 948 CCS values (594 positive and 354 negative ionization modes). We screened for the potential co-occurrence of interfering compounds originating from five different matrix backgrounds, leading to peaks with similar <i>m</i>/<i>z</i> and RT but differences in the mobilograms. For all matrices combined, 112 peaks with different mobility values relative to the reference standard were found. Our evaluation highlights the benefits of TIMS in reducing the number of inconclusive assignments through the separation of coeluting compounds and background noise and gaining a high MS² coverage for low-abundant ions. These advantages are beneficial especially for suspect screening applications, where broader RT windows are necessary.