Workflow-development for analyzing per- and polyfluoroalkyl substances with HPLC-FT-ICR-MS

Per- and polyfluoroalkyl substances (PFAS) are of significance due to their wide range of applications, high chemical persistence and their ability to bioaccumulate and harm human health and the environment. Hence, highly sensitive analytical methods are needed for the ultra-trace analyses of these molecules. Here, High Performance Liquid Chromatography (HPLC) coupled with Fourier-Transform Ion Cyclotron Resonance Mass Spectrometry (FT-ICR-MS) using Electrospray Ionization (ESI) in negative mode was used to detect the twenty PFAS regulated by EU 2020/2184. Samples were purified by solid phase extraction (SPE) and evaporated under nitrogen to a 1 mL extract. Two complementary workflows are presented. The first identifies all 20 PFAS in a single chromatogram with a peak resolution above 1.2 each in under 10 min. The second uses direct injection combined with Extracted Ion Chromatograms (EICs) for single-species screening. A buffer-free configuration reached an on-column LOD of approximately 0.01 ng, corresponding to a sample-side LOD of 1 ng/L per analyte after the 1000-fold preconcentration inspired by FprEN 17,892:2023. The trade-off between chromatographic resolution and ESI sensitivity introduced by ion-pair buffers is quantified and the performance of FprEN 17,892:2023 when interfaced with high-resolution rather than tandem MS is assessed. Finally, an efficient method for sample preparation of PFAS-containing water samples is described.