Ultrashort to Ultralong: An Extensive LC-MS/MS Method for Human Serum PFAS Biomonitoring

Abstract

Per- and poly-fluoroalkyl substances (PFAS) are a group of compounds largely used to make commercial products grease-, water-, and stain-resistant. PFAS have a range of utility, making surfaces low friction, providing protective barriers in firefighter turnout gear and stain-resistant clothing, and acting as surfactants in aqueous film forming foam used to fight liquid-fuel fires. Many PFAS have been associated with a range of adverse health effects including cancers, endocrine disruption, liver disease, and dyslipidemia. Long-chain PFAS (PFAS with ≥8 carbons) are considered legacy chemicals because they have been phased out of use and replaced with shorter chain (2-6 carbons) PFAS. As the types of PFAS used in products change, the need to develop analytical methods that accurately quantify emerging PFAS is amplified. We present a liquid chromatography-tandem mass spectrometry method for extraction and quantification of 58 PFAS in human serum, ranging from ultrashort- to ultralong-chain using isotope dilution calibration. Our analytical method is the first to successfully analyze such a wide range of PFAS in human serum, that vary in both structure and chain-length. The method has high precision (relative standard deviation <20%) and accuracy (80%–120%) for most analytes (up to 99%) and limits of quantification ≤0.2 ng/mL serum for 95% of target analytes. This method was applied to human serum samples, and the results demonstrated that while legacy PFAS were detected at a high frequency and made up a large portion of the PFAS composition in serum, when the ultrashort-chain PFAS were detected, they dominated the total serum PFAS burden.