A practical and robust method for quantification of long-chain PFAS in food matrices using ¹⁸O-water-based generation...

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are persistent organic contaminants of global concern. In response to increasingly stringent international regulations, including the addition of long-chain perfluoroalkyl carboxylic acids (LC-PFCA) to the Stockholm Convention in 2025, accurate monitoring of these compounds in food matrices is essential for assessing human exposure. Although analytical methods for PFAS in drinking water are well established, reliable quantification of LC-PFAS in foods remains challenging because of matrix complexity, strong adsorption of long-chain compounds, and the limited availability of suitable isotope-labeled internal standards. Here, we report a robust and traceable strategy for the accurate quantification of LC-PFAS (C ≥ 10) in food matrices. Building on a comprehensive PFAS measurement framework covering homologues from C4 to C18, we addressed key analytical limitations by introducing an ¹⁸O-labeling approach for carboxylic acid compounds to compensate for gaps in commercially available internal standards. The isotopic purity and stability of the labeled compounds were systematically validated. In addition, a liquid-liquid extraction procedure combined with C8 reversed-phase chromatography minimized analyte loss resulting from strong hydrophobic adsorption, enabling accurate, precise, and sensitive determination of LC-PFAS. This method provides a practical, cost-effective, and reliable analytical approach for routine LC-MS/MS analysis and supports improved food monitoring and long-term exposure assessment.