Uncovering PFAS and halogenated chemicals using nontargeted analysis and the PFAS IMplementer for mass spectrometry (PIMMS).

Per- and polyfluoroalkyl substances (PFASs) are synthetic chemicals of considerable epidemiological concern. While targeted liquid chromatography (LC)-tandem mass spectrometry (MS/MS) methods are established for legacy PFAS, emerging replacement compounds require nontargeted analysis (NTA) for comprehensive characterization. However, NTA of complex biological matrices like human serum is analytically challenging because of the presence of many endogenous interferences and unknown PFAS molecules. To address this, ion mobility spectrometry has been coupled with LC and MS (LC-IMS-MS). This approach provides orthogonal separation via collision cross section to resolve isobars and filter noise. Despite its utility, current software lacks efficient PFAS feature prioritization, requiring extensive manual curation. We developed the PFAS IMplementer for Mass Spectrometry (PIMMS), a vendor-neutral, open-source tool that uses advanced filtering and scoring algorithms for rapid LC-IMS-MS data analysis. The potential utility of PIMMS was demonstrated using serum from bovine and human populations. PIMMS could identify both legacy and novel PFAS in addition to eight halogenoalkane xenobiotics (containing bromine, chlorine, and iodine). Of note, these halogenoalkane species were often only singly or doubly halogenated and were still effectively prioritized by PIMMS demonstrating the potential to identify a potentially growing number of novel compounds with only a single degree of halogenation.