Development, validation, and clinical assessment of a liquid chromatography-tandem mass spectrometry serum assay for per- and polyfluoroalkyl substances (PFAS) recommended by the National Academies of Science, Engineering, and Medicine (NASEM)

Per- and polyfluoroalkyl substances (PFAS) are widely used in industry, residential, and consumer products. Studies have shown associations between high PFAS exposure and adverse health effects. In 2022, the National Academies of Science, Engineering, and Medicine (NASEM) published Guidance on PFAS Exposure, Testing, and Clinical Follow-up providing laboratory and clinical direction. The Guidance suggests nine PFAS should be measured in serum or plasma specimens and summed to provide a total PFAS concentration using a NASEM-recommended method. Follow-up clinical recommendations are based on the calculated PFAS NASEM summation. We developed and validated a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method in accordance with NASEM recommendations but distinguished by the ability to separate closely related structural isomers. As part of our validation, PFAS prevalence was evaluated in a population survey comprised of clinical donor and remnant specimens (n = 1023 in total). In this study, 82.2% of the specimens had PFAS NASEM summations of 2 to < 20 ng/mL and 2.5% had a summation ≥ 20 ng/mL. The median PFAS NASEM summation was 4.65 ng/mL in this study, lower than the 7.74 ng/mL median observed in the 2017-2020 Centers for Disease Control and Prevention, National Health and Nutrition Examination Survey (n = 3072). This lower median PFAS NASEM summation may reflect a decline in PFAS population levels over time or sample population exposure differences.