Evaluation of isotope-dilution mass spectrometry, internal standard, and external standard methods for PFAS...

Accurate quantification of per- and polyfluoroalkyl substances (PFAS) in environmental matrices is crucial for reliable exposure assessment but remains challenging owing to low concentrations and matrix-induced variability. In this study, three calibration approaches, external standard (ES), internal standard (IS), and isotope dilution mass spectrometry (IDMS), were systematically evaluated for the determination of perfluorohexanesulfonic acid (PFHxS), perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and perfluorononanoic acid (PFNA) in fortified tap water and fortified soil. Linearity of calibration curves was assessed across five concentration levels for each analyte. IDMS consistently demonstrated the highest linearity (coefficient of determination R² of 0.999) for all target analytes, followed by IS. ES displayed acceptable linearity, although the performance was slightly lower in soil matrices, with R² ranging from 0.992 to 0.996. Accuracy was evaluated using measured-to-assigned concentration ratios in spiked tap water. IDMS yielded ratios of 0.96-1.07 with small standard deviations, demonstrating high trueness. When IDMS was used as the reference, IS and ES showed matrix- and analyte-dependent biases. In tap water, IS improved agreement with IDMS relative to ES but still overestimated PFOS, PFOA, and PFNA, whereas ES showed the largest positive bias. In soil, IS produced values close to those of IDMS for all analytes, while ES exhibited greater variability and occasional underestimation. Overall, IDMS enabled the most consistent and reliable quantification across matrices. These results highlight the importance of isotope dilution calibration using structurally matched mass-labeled standards and indicate that IS and ES methods require careful consideration of matrix effects and surrogate selection.