Filling the Gaps in PFAS Detection: Integrating GC-MS Non-Targeted Analysis for Comprehensive Environmental Monitoring and Exposure Assessment.

Per- and polyfluoroalkyl substances (PFAS) are globally recognised as persistent organic pollutants of substantial environmental and public health concern as a result of their toxicity, bioaccumulation, and chemical stability. The detection of PFAS at trace and ultra-trace levels in complex matrices remains an analytical challenge due to the presence of numerous unknown analogues and the diverse physicochemical properties of PFAS. This systematic review critically evaluates 55 peer-reviewed studies published between 2010 and 2025 that focus on analytical techniques for quantifying and identifying PFAS in environmental and biological samples. The assessment follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and compares the performance of major analytical platforms, including liquid chromatography tandem mass spectrometry (LC–MS/MS), ultra-high-performance liquid chromatography high-resolution mass spectrometry (UHPLC–HRMS), gas chromatography mass spectrometry (GC–MS), extractable/adsorbable organofluorine (EOF/AOF), surface-enhanced Raman spectroscopy (SERS), and electrochemical or hybrid sensor-based approaches. LC–MS/MS and UHPLC–HRMS remain the gold standards for quantitative and non-target PFAS analysis, respectively, while emerging spectroscopic and electrochemical methods offer rapid, portable, and cost-effective alternatives. Molecularly imprinted polymers, deep eutectic solvents, and bubble-assisted extraction are among the sample preparation advancements that have further enhanced environmental sustainability and sensitivity. The review highlights the need for standardized QA/QC protocols, certified reference materials, and inter-laboratory harmonization. Integration of artificial intelligence, green chemistry, and multi-platform detection systems represents the future direction for comprehensive PFAS monitoring and exposure assessment. Keywords: Per- and Polyfluoroalkyl Substances, Mass Spectroscopy, Non-target analysis, Surface-Enhanced Raman Spectroscopy, Environmental monitoring.

This work was in response to the Defense Logistic Agency’s (DLA) Subsistence Network Broad Agency Announcement, BAA-0003-16 addressing 2019 NDAA Section 329 that states packaging materials used for Meals Ready-to-Eat (MRE) that contact food products must be free of per- and polyfluoroalkyl substances (PFAS). This was addressed by determining the presence or absence of PFAS on MREs by extraction followed by gas chromatography mass spectrometry (GC-MS) and liquid chromatography tandem mass spectrometry (LC-MS/MS). Any samples positive for PFAS were quantitated using LC triple quadrupole (QqQ) MS at the US Army Engineering and Research Development Center (ERDC) and by high resolution quadrupole time-of-flight (qTOF) MS and GC-MS at Oregon State University (OSU).

Per- and poly-fluoroalkyl substances (PFAS) have gained much attention recently due to their high persistence and potential health risks. PFAS are often used in the fabrication of various consumer products, such as firefighting foam, non-stick utensils, water-repellent clothes, stain-resistant materials, and food packaging products. PFAS are highly stable and persistent due to their strong carbon-fluorine bonds and have been found to be absorbed in humans and animals for significant amount of time. Studies have shown that drinking water may act as a reservoir of trace level PFAS and contribute to the accumulation of PFAS in human bodies, which may lead to adverse health issues in liver, kidney, and reproductive systems. However, limited studies have been done to remove trace level PFAS in point-of-use (POU) water treatment systems, including reverse osmosis (RO) and activated carbon (AC) systems. The objective of this study was to evaluate PFAS removal in POU systems and factors that may impact PFAS removal efficiencies. Mixtures of perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS), and perfluorobutane sulfonic acid (PFBS) under two different concentrations (1 μg/l and 10 μg/l) were spiked into tap water and PFAS removal efficiencies in three RO and three AC systems were evaluated. Solid phase extraction coupled with liquid chromatography tandem mass spectrometry (SPE-LC/MS/MS) was used to quantify trace level PFAS concentrations. The results showed that PFAS were effectively removed in both RO and AC systems with average removal efficiencies greater than 90% in all tested POU systems. Among the three evaluated PFAS with different chain-lengths (PFOS: 8 carbons, PFHxS: 6 carbons, PFBS: 4 carbons), higher removal efficiencies were observed in long-chain perfluoroalkyl sulfonic acids (carbon chain-length ≥ 6), while relatively low removal efficiency and high variability was observed in PFBS removal. These results suggest that POU systems are generally effective to remove PFAS, but short-chain PFBS may not be consistently removed, even though they have been frequently used as alternative PFAS to replace conventional long-chain PFAS. The results from this study may improve the understanding of PFAS removal in POU systems and provide useful information for the design, operation, and maintenance of POU systems to minimize health risks of PFAS in drinking water.

Chapter 14 - Analysis of GenX and Other Per- and Polyfluoroalkyl Substances in Environmental Water Samples

Per- and polyfluoroalkyl substances (PFAS) are a class of thousands of man-made chemicals that are persistent and highly stable in the environment. Fish consumption has been identified as a key route of PFAS exposure for humans. However, routine fish monitoring targets only a handful of PFAS, and non-targeted analyses have largely only evaluated fish from heavily PFAS-impacted waters. Here, we evaluated PFAS in fish fillets from recreational and drinking water sources in central North Carolina to assess whether PFAS are present in these fillets that would not be detected by conventional targeted methods. We used liquid chromatography, ion mobility spectrometry, and mass spectrometry (LC-IMS-MS) to collect full scan feature data, performed suspect screening using an in-house library of 100 PFAS for high confidence feature identification, searched for additional PFAS features using non-targeted data analyses, and quantified perfluorooctanesulfonic acid (PFOS) in the fillet samples. A total of 36 PFAS were detected in the fish fillets, including 19 that would not be detected using common targeted methods, with a minimum of 6 and a maximum of 22 in individual fish. Median fillet PFOS levels were concerningly high at 11.6 to 42.3 ppb, and no significant correlation between PFOS levels and number of PFAS per fish was observed. Future PFAS monitoring in this region should target more of these 36 PFAS, and other regions not considered heavily PFAS contaminated should consider incorporating non-targeted analyses into ongoing fish monitoring studies.

Temporal variations of perfluoroalkyl substances and polybrominated diphenyl ethers in alpine snow

Side-chain fluorotelomer-based polymers in children car seats.

When Chemicals Go to the Dark Side

Non-targeted analysis (NTA) and suspect screening analysis (SSA) are powerful techniques that rely on high-resolution mass spectrometry (HRMS) and computational tools to detect and identify unknown or suspected chemicals in the exposome. Fully understanding the chemical exposome requires characterization of both environmental media and human specimens. As such, we conducted a review to examine the use of different NTA and SSA methods in various exposure media and human samples, including the results and chemicals detected. The literature review was conducted by searching literature databases, such as PubMed and Web of Science, for keywords, such as “non-targeted analysis”, “suspect screening analysis” and the exposure media. Sources of human exposure to environmental chemicals discussed in this review include water, air, soil/sediment, dust, and food and consumer products. The use of NTA for exposure discovery in human biospecimen is also reviewed. The chemical space that has been captured using NTA varies by media analyzed and analytical platform. In each media the chemicals that were frequently detected using NTA were: per- and polyfluoroalkyl substances (PFAS) and pharmaceuticals in water, pesticides and polyaromatic hydrocarbons (PAHs) in soil and sediment, volatile and semi-volatile organic compounds in air, flame retardants in dust, plasticizers in consumer products, and plasticizers, pesticides, and halogenated compounds in human samples. Some studies reviewed herein used both liquid chromatography (LC) and gas chromatography (GC) HRMS to increase the detected chemical space (16%); however, the majority (51%) only used LC-HRMS and fewer used GC-HRMS (32%). Finally, we identify knowledge and technology gaps that must be overcome to fully assess potential chemical exposures using NTA. Understanding the chemical space is essential to identifying and prioritizing gaps in our understanding of exposure sources and prior exposures.Impact statementThis review examines the results and chemicals detected by analyzing exposure media and human samples using high-resolution mass spectrometry based non-targeted analysis (NTA) and suspect screening analysis (SSA).

A systematic review for non-targeted analysis of per- and polyfluoroalkyl substances (PFAS).

BACKGROUND AND AIM: Non-targeted metabolomics has been incorporated into recent epidemiological studies to investigate metabolic mechanisms underlying adverse health effects of per-fluoroalkyl and polyfluoroalkyl substances (PFAS) exposure. The purpose of this review is to summarize the application of non-targeted metabolomics in epidemiological studies that assessed metabolite and metabolic pathway alterations associated with PFAS exposure. METHODS: We performed a scoping review of human studies that conducted non-targeted metabolomics and PFAS analyses including original articles published in PubMed before March 1, 2021. We summarized the study characteristics and the metabolites and metabolic pathways reported to be associated with PFAS exposure. RESULTS:Nine human studies published between 2018 to 2021 were identified. The study sample ranged from 40 to 965 participants, including children and adolescents (n=3), adults (n=3), or pregnant women (n=3). Health outcomes involved included non-alcoholic liver, type 2 diabetes and other cardiometabolic outcomes. Liquid chromatography–mass spectrometry was the primary analytical platform for PFAS measurement and non-targeted metabolomics. PFAS levels were measured in plasma (n=5) or serum (n=4), while the metabolomic profiles were generated in plasma (n=5), serum (n=3), or urine (n=1). The most studied PFAS compounds were PFOS (n=9), PFOA (n=8), PFHxS (n=8), PFNA (n=5), and PFAS mixtures (n=4). Among seven studies that conducted pathway enrichment analysis, the most commonly reported metabolic pathways affected by multiple PFAS compounds were lipid metabolism, including glycerophospholipid, glycosphingolipid, and linoleate metabolism, followed by amino acid-related pathways, such as urea cycle/amino group metabolism, alanine and aspartate metabolism, and beta-alanine metabolism. Other reported metabolomics alterations possibly associated with PFAS include carbohydrate-related metabolism, xenobiotic (drug) related metabolism, and vitamin metabolism. CONCLUSIONS:Multiple PFAS exposures were associated with alterations to lipid- or amino acid-related metabolism in human studies that used non-targeted metabolomics. Whether these PFAS-associated biological changes lead to adverse health risks requires further research. KEYWORDS: PFAS, Metabolomics, Chemical exposures, Obesity and metabolic disorders

Per- and polyfluoroalkyl substances (PFAS) are widely used persistent synthetic chemicals that have been linked to adverse health effects. While the behavior of PFAS has been evaluated in the environment, our understanding of reaction products in mammalian systems is limited. This study identified biological PFAS transformation products and generated mass spectral libraries to facilitate an automated search and identification. The biological transformation products of 27 PFAS, spanning 5 chemical subclasses (alcohols, sulfonamides, carboxylic acids, ethers, and esters), were evaluated following enzymatic reaction with mouse liver S9 fractions. Four major pathways were identified by liquid chromatography-high-resolution mass spectrometry: glucuronidation, sulfation, dealkylation, and oxidation. Class-based fragmentation rules and associated PFAS transformation product libraries were generated and integrated into an automated nontargeted PFAS data analysis software (FluoroMatch). Fragmentation was additionally predicted for the potential transformation products of more than 2,500 PFAS in the EPA CompTox Chemicals Dashboard PFASSTRUCTv4. Generated mass spectral libraries were validated by applying FluoroMatch to a data set of urine from aqueous film-forming foam (AFFF)-dosed mice. Toxicity predictions showed identified PFAS transformation products to be potential developmental and mutagenic toxicants. This research enables more comprehensive PFAS characterization in biological systems, which will improve the assessment of exposures and evaluation of the associated health impacts.

Papers and textiles that are treated with per- and polyfluoroalkyl substances (PFASs) are sources of human and environmental exposure. Data for individual PFASs, such as perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA), are not placed into the context of total fluorine for papers and textiles. Gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) were used to quantify volatile and ionic PFASs, respectively, and the total oxidizable precursor (TOP) assay was used to quantify precursors that form perfluoroalkyl carboxylates. Molar sums of PFASs obtained by GC-MS, LC-MS/MS, and precursors were compared to total fluorine (nmol F/cm2) determined by particle-induced gamma ray emission (PIGE) spectroscopy, measured before and after extraction. Volatile and ionic PFASs and unknown precursors accounted for 0-2.2%, 0-0.41%, and 0.021-14%, respectively, of the total nmol F/cm2 determined by PIGE. After extraction, papers and textiles retained 64 ± 28% to 110 ± 30% of the original nmol F/cm2 as determined by PIGE, indicating that the majority of fluorine remains associated with the papers and textiles. The sum of PFASs in the volatile, ionic, and precursor fraction, and total fluorine after extraction indicate that mass balance was achieved (within analytical error) of the initial total fluorine measured by PIGE.

Analysis of per-and polyfluorinated alkyl substances by chromatography-mass spectrometry: A review.

Non-target and target screening and risk assessment of per- and polyfluoroalkyl substances in textile wastewater and receiving river