Communicating Confidence of Per- and Polyfluoroalkyl Substance Identification via High-Resolution Mass Spectrometry

Abstract

Per- and polyfluoroalkyl substances (PFASs) are important environmental contaminants, yet relatively few analytical reference standards exist for this class. Nontarget analyses performed by means of high-resolution mass spectrometry (HRMS) are increasingly common for the discovery and identification of PFASs in environmental and biological samples. The certainty of PFAS identifications made via HRMS must be communicated through a reliable and harmonized approach. Here, we present a confidence scale along with identification criteria specific to suspect or nontarget analysis of PFASs by means of nontarget HRMS. Confidence levels range from level 1a-"Confirmed by Reference Standard," and level 1b-"Indistinguishable from Reference Standard," to level 5-"Exact Masses of Interest," which are identified by suspect screening or data filtering, two common forms of feature prioritization. This confidence scale is consistent with general criteria for communicating confidence in the identification of small organic molecules by HRMS (e.g., through a match to analytical reference standards, library MS/MS, and/or retention times) but incorporates the specific conventions and tools used in PFAS classification and analysis (e.g., detection of homologous series and specific ranges of mass defects). Our scale clarifies the level of certainty in PFAS identification and, in doing so, facilitates more efficient identification.

Figure 1

(a) 1-UPFOS (CID 162420437) and (b) 2-UPFOS (CID 162420438) are (tail) positional isomers which differ by the position of the same functional group (i.e., unsaturated bond), whereas UPFOS and (c) PFEtCHxS (CID 101650) are constitutional isomers with distinct functional groups.

Figure 2

(a) CEtAmPr-FBSA (CID 139595456) and (b) AmPr-FBSA-PrA (CID 162420439) are (headgroup) positional isomers which differ by the position of the highlighted propanoic acid group.

Figure 3

Mass spectra for (a, c) UPFOS and (b, d) PFEtCHxS collected via QTOF-MS with collision-induced dissociation at 10 and 40 eV. UPFOS spectrum collected from liver tissue of mouse dosed with aqueous film-forming foam (AFFF). PFEtCHxS spectrum collected from vehicle mouse liver tissue spiked with PFEtCHxS.