Multidimensional-Constrained Suspect Screening of Hydrophobic Contaminants Using Gas Chromatography-Atmospheric Pressure Chemical Ionization-Ion Mobility-Mass Spectrometry

Suspect screening strives to rapidly monitor a large number of substances in a sample using mass spectral libraries. For hydrophobic organic contaminants (HOCs), these libraries are traditionally based on electron ionization mass spectra. However, with the growing use of state-of-the-art mass spectrometers, which often use alternative ionization approaches and separation techniques, new suspect screening workflows and libraries are urgently needed. This study established a new suspect screening library for 1,590 HOCs, including exact mass and a combination of measured and model-predicted values for retention time (RT) and collision cross section (CCS). The accuracy of <i>in silico</i> predictions was assessed using standards for 102 HOCs. Thereafter, using gas chromatography-atmospheric pressure chemical ionization-ion mobility-mass spectrometry, a suspect screening workflow constrained by the full scan mass spectrum of (quasi-)molecular ions (including isotope patterns), RT, CCS, and fragmentation mass spectra, together with a continuous scoring system, was established to reduce false positives and improve identification confidence. Application of the method to fortified and standard reference sediment samples demonstrated true positive rates of 79% and 64%, respectively, with all false positives attributed to suspect isomers. This study offers a new workflow for improved suspect screening of HOCs using multidimensional information and highlights the need to enrich mass spectral databases and extend the applicable chemical space of current <i>in silico</i> tools to hydrophobic substances.