Trapped ion mobilty improves annotation accuracy in LC-HRMS screening applications for exposomics

The widespread use of a large number of chemicals results in a significant exposure of humans and the environment, posing potential risks to human health and ecosystems. To assess the exposure to chemical mixtures, screening applications covering a large number of analytes based on liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS) are required. False positives occur frequently in complex environmental and biological matrices due to the interference of ions with the same or a close m/z, stemming from isomeric and isobaric compounds, chemical noise, in-source fragmentation, or adduct formation. Besides that, interferences may also result in false negatives, especially when only trace levels are present. Due to an insufficient separation in the LC dimension, MS2 spectra may contain fragments from other analytes within the precursor isolation window, leading to decreased spectral matching values. In recent years, ion mobility separation (IM), and later on trapped ion mobility mass spectrometry (TIMS) was introduced as an additional separation dimension in HRMS. We developed a IM-target screening method and evaluated for a set of more than 700 chemicals of interest if the TIMS separation allowed for a separation of interfering ions as compared to the classical LC-HRMS method in different matrices.