Quantitative Spatial Analysis of PFAS in Nine Biological Tissues from Mouse via MALDI-TIMS-MSI

Per- and polyfluoroalkyl substances (PFASs) are a persistent and widespread class of synthetic chemicals that have been detected throughout the environment. Due to their ubiquity, persistence, and mobility, PFAS can undergo biomagnification. Absorption and distribution of these chemicals in different tissues are key factors in understanding how they become biomagnified and induce adverse health effects. The spatial exposomics of legacy or emerging contaminants and their accumulation in biological tissues via mass spectrometry imaging (MSI) is an interesting alternative to facilitate such studies. In this study, we aimed to develop an in situ analytical method that is fast, reproducible, and cost-effective to simultaneously detect, localize, and quantify a list of 24 PFAS in nine different tissues from male mouse samples while using PFOS as a representative case study for the in vivo study. The optimized protocol was used to maximize ionization efficiency of PFAS while using matrix-assisted laser desorption ionization (MALDI) coupled with trapped ion mobility separation (TIMS) MSI. The effect of ammonium fluoride as an additive to the MALDI matrix (1,5-diaminonaphthalene, DAN) was evaluated, providing a cost-effective ionization agent with a limit of detection of 17.20 fmol/mm². Ion mobility separation significantly enhanced the sensitivity. This approach offers a rapid, high-throughput, and spatially resolved analysis of 24 PFAS in brain, spleen, testis, heart, intestine, thyroid, kidney, pancreas, and liver tissues; presenting a powerful tool for future environmental and toxicological studies.