Serum untargeted lipidomic characterization in a general Chinese cohort with residual per-/polyfluoroalkyl substances by liquid chromatography-drift tube ion mobility-mass spectrometry.

Per- and polyfluoroalkyl substances (PFAS) remain controversial due to their high persistency and potential human toxicity. Although occupational exposure to PFAS has been widely investigated, the implications of PFAS occurrence in the general population remain to be unraveled. Considering that serum from most people contains PFAS, the aim of this study was to characterize the lipidomic profile in human serum from a general cohort (n = 40) with residual PFAS levels. The geometric means of ∑PFAS (11.8 and 4.4 ng/mL) showed significant differences (p < 0.05) for the samples with the highest (n = 20) and lowest (n = 20) concentrations from the general population respectively. Reverse-phase liquid chromatography coupled to drift tube ion mobility and high-resolution mass spectrometry using dual polarity ionization was used to characterize the lipid profile in both groups. The structural elucidation involved the integration of various parameters, such as retention time, mass-to-charge ratio, tandem mass spectra and collision cross section values. This approach yielded a total of 20 potential biomarkers linked to the perturbed glycerophospholipid metabolism, energy metabolism and sphingolipid metabolism. Among these alterations, most lipids were down-regulated and some specific lipids (PC 36:5, PC 37:4 and PI O-34:2) exhibited a relatively strong Spearman correlation and predictive capacity for PFAS contamination. This study could support further toxicological assessments and mechanistic investigations into the effects of PFAS exposure on the lipidome.