Modern HPLC Applications in PFAS Food Analysis: Technological Progress and Regulatory Implications

High-performance liquid chromatography (HPLC) has emerged as a cornerstone analytical technique in the detection and quantification of per- and polyfluoroalkyl substances (PFAS) in food. PFAS are synthetic compounds widely used in industrial and consumer products for their water- and grease-resistant properties. Their persistence in the environment and potential health risks have led to increased scrutiny and regulatory action. As food safety becomes a global priority, the role of HPLC in monitoring PFAS contamination has grown significantly. This article explores the technological advancements in HPLC, the pathways through which PFAS enter the food supply, the health implications of exposure, and the evolving regulatory landscape. It also discusses current challenges and future directions for PFAS analysis in food using HPLC.

Advancements in HPLC for PFAS Detection

Recent innovations in HPLC have significantly enhanced its capabilities for PFAS analysis. One of the most notable advancements is the development of high-efficiency columns. Core-shell columns, which consist of a solid core surrounded by a porous shell, offer improved separation efficiency and faster analysis times compared to traditional fully porous particles. Monolithic columns, made from a single piece of porous material, provide high permeability and low backpressure, enabling faster flow rates and shorter analysis times.³

Detection systems have also seen substantial improvements. Coupling HPLC with tandem mass spectrometry (LC-MS/MS) and high-resolution mass spectrometry (HRMS) allows for the detection of PFAS at parts-per-trillion (ppt) levels. These systems offer high sensitivity and specificity, which are essential for analyzing complex food matrices. The EPA’s Method 1633 utilizes reversed-phase HPLC with MS/MS to quantify 40 PFAS compounds across various environmental and food matrices.²

Sample preparation techniques have evolved to improve recovery rates and reduce matrix effects. Solid-phase extraction (SPE), dispersive liquid-liquid microextraction (DLLME), and QuEChERS are commonly used methods that have been refined for PFAS analysis. Automation of these processes has increased throughput and reproducibility, reducing the potential for human error.¹

PFAS Migration from Food Packaging

PFAS are commonly used in food contact materials (FCMs) such as paper, plastic, and coated metals due to their grease- and water-resistant properties. However, these substances can migrate into food, especially under conditions involving heat, fat, or acidity. A systematic review identified 68 PFAS compounds in food packaging materials, with long-chain PFAS still prevalent despite regulatory efforts to phase them out.⁴

Migration studies have shown that fatty and acidic foods are particularly susceptible to PFAS leaching from packaging. This has led to increased efforts to regulate PFAS in FCMs and to develop safer alternatives. The migration of PFAS from packaging into food poses a significant risk, especially when considering the cumulative exposure from multiple sources.

Health Implications of PFAS Exposure

Exposure to PFAS has been linked to a wide range of adverse health outcomes. These include developmental toxicity, endocrine disruption, immune suppression, liver and kidney damage, and increased risk of cancers such as kidney and testicular cancer. Human biomonitoring studies have consistently detected PFAS in serum, breast milk, and urine, indicating widespread exposure.¹

Long-chain PFAS, such as PFOA and PFOS, are particularly concerning due to their bioaccumulative nature and long half-lives in human tissues. Emerging short-chain alternatives, such as GenX and PFBS, may also pose significant health risks, although data on their toxicity are still limited. Vulnerable populations, including infants and pregnant women, are at heightened risk due to the potential for developmental and reproductive effects.

Regulatory Landscape: U.S. and EU Approaches

The regulatory response to PFAS contamination has varied across regions, with the United States and the European Union taking distinct approaches.

In the United States, the Environmental Protection Agency (EPA) finalized enforceable Maximum Contaminant Levels (MCLs) for six PFAS in drinking water in April 2024. These include PFOA and PFOS at 4 ppt, and PFHxS, PFNA, and HFPO-DA (GenX) at 10 ppt. Public water systems are required to complete initial monitoring by 2027 and implement treatment solutions by 2029 if MCLs are exceeded.²

The FDA has also taken steps to regulate PFAS in food packaging, banning certain PFAS compounds and increasing monitoring efforts. These actions reflect a growing recognition of the need to protect public health from PFAS exposure through the food supply.

In the European Union, the European Chemicals Agency (ECHA) has proposed a comprehensive restriction on PFAS under the REACH framework. Regulation (EU) 2022/2388 sets maximum levels for PFOS, PFOA, PFNA, and PFHxS in various foodstuffs. The EU Drinking Water Directive also establishes strict limits for PFAS, aiming to harmonize standards across member states.⁵

Challenges and Future Directions

Despite significant progress, several challenges remain in the analysis of PFAS in food using HPLC. One major challenge is the complexity of food matrices, which often require extensive cleanup to reduce interference. Analytical gaps also exist, as many PFAS lack certified reference materials, making quantification difficult.

Regulatory fragmentation is another issue, with different countries setting varying limits for PFAS in food. This lack of harmonization complicates compliance and enforcement efforts. There is a need for global standards to ensure consistent protection of public health.

Future research should focus on expanding PFAS analyte libraries, developing rapid and cost-effective screening tools, and investigating the toxicology of emerging PFAS. Harmonizing international regulatory frameworks will be essential for effective management of PFAS contamination in the food supply.

Conclusion

HPLC continues to play a critical role in the detection and quantification of PFAS in food. Technological advancements in column design, detection systems, and sample preparation have significantly improved analytical performance. As regulatory frameworks evolve, robust and validated methods will be essential for ensuring food safety and protecting public health.

The persistence and toxicity of PFAS underscore the importance of continued investment in analytical capabilities and regulatory oversight. By addressing current challenges and pursuing future research directions, the scientific and regulatory communities can work together to mitigate the risks associated with PFAS in the food supply.

References

Dehghani, M. H., et al. (2025). An Insight into the Environmental and Human Health Impacts of PFAS: Exploring Exposure Pathways and Their Implications. Environmental Sciences Europe, 37, Article 81. https://doi.org/10.1186/s12302-025-01122-9
EPA. (2024). Final Rule: National Primary Drinking Water Regulation for PFAS. Federal Register. https://www.epa.gov/sdwa/and-polyfluoroalkyl-substances-pfas
McHale, C. (2025). Current LC/MS Approaches for PFAS Analysis with Ultrashort and Long Chain Mixtures. Advanced Materials Technology. https://halocolumns.com/wp-content/uploads/2025/03/AMT_TR_02_2025_PFAS_final-1.pdf
Phelps, D. W., et al. (2024). Per- and Polyfluoroalkyl Substances in Food Packaging: Migration, Toxicity, and Management Strategies. Environmental Science & Technology, 58(10), 5670–5684. https://doi.org/10.1021/acs.est.3c03702
Williams, J. L., & Wold, C. (2025). How the EU & U.S. Tackle the Regulatory Challenges of PFAS. American Journal of Heterocyclic Chemistry, 10(2), 55–70. https://doi.org/10.11648/j.ajhc.20251002.13