Ion Mobility-Constrained Nontargeted Screening of PFAS in Complex Environmental Matrices Using 18-T FTICR Mass Spectrometry.

Abstract

Reliable screening of per- and polyfluoroalkyl substances (PFASs) in complex environmental matrices remains challenging due to severe spectral congestion and matrix-derived interferences under nontargeted conditions. Accurate-mass criteria from high-resolution mass spectrometry (HRMS) alone are often insufficient to suppress putative PFAS candidates arising from natural organic matter (NOM), leading to elevated false-positive rates. Here, we develop a mobility-resolved PFAS screening strategy by integrating direct-infusion gated trapped ion mobility spectrometry with Fourier transform ion cyclotron resonance mass spectrometry (gTIMS FTICR MS). By defining the mobility-resolved chemical space and characteristic mobility behavior of PFAS reference standards, ion mobility is implemented as a physically based decision constraint rather than a supplementary descriptor. Evaluation across chemically diverse NOM systems and environmental samples (e.g., landfill leachate and wastewater) demonstrates that enforcing mobility-m/z consistency reduces the space of putative PFAS candidates by more than 90% relative to mass-only screening. The mobility constraint further enables discrimination of near-isobaric interferences differing by only a few millidaltons (e.g., 2.54 mDa) and supports higher-confidence prioritization of PFAS candidates through agreement with homologous mobility trends. Rather than aiming for definitive structural identification, this work establishes a transferable mobility-constrained screening framework that improves the reliability of nontargeted PFAS detection in complex environmental matrices.