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Typical Challenges for PFAS Analysis

(04.03.2025)


PFAS, also sometimes called the “Forever Chemicals” due to their exceptionally long half-lives, are a growing environmental concern. Their extreme persistence in the natural environment combined with their association to potential adverse health effects requires that their presence is rigorously monitored. With proper monitoring, scientists can help to mitigate their impact on local ecosystems and the wider environment. However, in practical terms, doing this kind of PFAS monitoring still poses significant challenges for analysts.


1. Sheer number and diversity of PFAS: There are thousands of PFAS compounds, each with varying chemical structures and properties.

  • The CompTox database, maintained by the US Environmental Protection Agency, currently lists nearly 15,000 unique PFAS in its chemical structure listings.
  • The OECD (Organisation for Economic Co-operation and Development) now defines PFAS broadly as fluorinated substances that contain at least one fully fluorinated carbon atom. According to this OECD definition, the number of PFAS compounds is closer to 7 million (see PubChem Classification Browser).
  • Diversity of compounds: This diversity complicates the development of standardized methods for their detection and quantification.  Standard methods may only detect a small subset, meaning many "hidden" PFAS go unmeasured. Developing methods that can comprehensively identify all these compounds is a major hurdle. Although workflows are being developed to help scientists with advancing PFAS identification, the enormous number of compounds and their varying properties can be overwhelming.
2. Sample Contamination: PFAS are found in many everyday products, which can lead to contamination of samples during collection and analysis. 
  • Cross-contamination can occur from multiple solvents, lab instruments, sampling tools, (FEP, PFA, PTFE) vessels, caps, septa, vials, Teflon tubing, separation columns, PFAS-coated items like gloves or clothing being used by the analyst in the laboratory or even skin products worn by the analyst. 
  • Ensuring clean and uncontaminated samples is a significant challenge.  By understanding the sources of the blank contamination based on a robust series of blank samples makes it easier to solve issues as they arise. So if you can’t get a clean blank, you’ll never get down to the very low detection levels required.
3. Ultra-low detection limits
  • Sensitivity is a big problem, since the presence of PFAS should be tested down to nanogram per liter, so analytical methods must be incredibly sensitive. 
  • This requires advanced equipment like high-resolution mass spectrometry (HRMS) or liquid chromatography-tandem mass spectrometry (LC-MS/MS).

4. Limited Reference Standards:
  • The availability of reference standards for many PFAS compounds is limited, making it difficult to accurately quantify their presence in samples.

5. Lack of standardized methods
  • While some regulatory agencies (like the US EPA and the EU) have developed methods for certain PFAS in water and soil, there’s no universal standard for testing across all matrices — such as food, air, or human tissue. 
  • This inconsistency complicates data comparison between studies.
6. Complex sample matrices
  • PFAS analysis isn't limited to water. Samples can include blood, soil, sediment, and biota — each presenting its own matrix effects, requiring different extraction and cleanup processes. 
  • Analyzing fatty matrices (like fish or dairy) is particularly tricky due to interference from lipids.

7. Emerging "precursors" and unknown PFAS
  • Many PFAS can transform in the environment, producing precursor compounds or degradation products. 
  • Some tests may miss these intermediates, underestimating the true PFAS burden. Analytical methods must evolve to capture these indirect contaminants.

8. Data Reduction
  • Vast quantities of data must be processed through peak picking and alignment, matched to databases, and undergo background subtracting and distilling into a concise report of findings.
  • There is no substitute for manual annotation to ensure the highest degree of confidence in the results.

9. Costs and expertise
  • PFAS analysis demands specialized, high-cost equipment and skilled personnel. 
  • Smaller labs may struggle to afford the technology or maintain staff with the necessary expertise, limiting widespread monitoring.

10. Regulatory inconsistencies
  • Different countries and agencies define PFAS in varying ways, complicating how researchers choose target compounds and methods.
  • Evolving regulatory standards and guidelines for PFAS analysis require laboratories to continuously update their methods and equipment to stay compliant.
  • Harmonizing global standards remains a work in progress.

Michael Sperling

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