Targeted vs. Non-Targeted Testing: Strengthening PFAS Analysis with Modern Environmental LIMS Software

Dubbed “forever chemicals” for their notorious persistence, per- and polyfluoroalkyl substances (PFAS) have become an environmental and public health crisis, posing an urgent threat we can no longer ignore. These synthetic chemicals—used in everything from nonstick cookware and firefighting foam to food packaging and industrial applications—persist in the environment for decades, accumulating in soil, water supplies, and even the human body. According to the U.S. Geological Survey, nearly 45% of drinking water samples in the United States contain at least one type of PFAS, highlighting the urgent need for robust analytical methods to detect and mitigate exposure.

Despite growing regulatory efforts, the challenge remains daunting: current analytical regulations cover only 40 to 70 PFAS compounds, which is less than 1-2% of the total PFAS known to exist. This leaves a significant gap, meaning we are only scratching the surface of potential PFAS contamination. 

With the rapid expansion of the PFAS testing market, laboratories are under immense pressure to analyze higher volumes of samples faster while maintaining accuracy. Future-proofing laboratory operations requires strong collaboration with technology providers to implement a laboratory information management system (LIMS) that streamlines workflows, enhances data integrity, and improves testing efficiency.

This blog discusses how targeted and non-targeted PFAS testing, when integrated with a modern environmental LIMS, creates a powerful strategy for regulatory compliance, risk mitigation, and effective PFAS analysis.

Standard Analytical Methods for PFAS Analysis 

1. Drinking (Potable) Water

• Method 537.1 (2018/2020): Measures 18 PFAS, including HFPO-DA, in drinking water using Solid Phase Extraction (SPE) and Liquid Chromatography/Tandem Mass Spectrometry (LC/MS/MS). (Updated in 2020 with editorial changes only.)
• Method 537 (2009 – Historical): Measures 14 PFAS in drinking water. (Replaced by Method 537.1 in 2018.)
• Method 533 (2019): Measures 25 PFAS in drinking water using isotope dilution anion exchange SPE and LC/MS/MS.

2. Non-Potable Water & Environmental Media

• Method 8327 (2019): Measures 24 PFAS in non-drinking water (groundwater, surface water, wastewater) using external standard calibration and Multiple Reaction Monitoring (MRM) LC/MS/MS.
• Method 1633 (2024): Measures 40 PFAS in wastewater, surface water, groundwater, soil, biosolids, sediment, landfill leachate, and fish tissue. 

3. Air Emissions

• OTM-45: Measures 50 PFAS in air emissions from stationary sources, focusing on semivolatile and particulate-bound PFAS. (Open for scientific feedback.)
• OTM-50: Measures 30 volatile PFAS in air emissions from stationary sources using passivated stainless-steel canisters. (Open for scientific feedback.)

Targeted vs. Non-Targeted PFAS Analysis

The analysis of PFAS relies on two distinct yet complementary testing approaches: targeted and non-targeted analysis. Targeted testing ensures regulatory compliance by identifying specific, well-documented PFAS compounds, while non-targeted testing expands the detection scope by uncovering unknown contaminants that may pose emerging environmental and health risks. Together, these approaches form a comprehensive strategy for PFAS monitoring, helping laboratories address both current regulatory requirements and future research needs.

The Role of Targeted Testing in PFAS Analysis

Targeted testing is designed to detect and quantify specific PFAS compounds that have been identified as environmental hazards by regulatory agencies such as the U.S. Environmental Protection Agency (EPA). This approach follows standardized methods to measure PFAS concentrations in drinking water, wastewater, soil, and other environmental media, ensuring compliance with public health guidelines.

Key Features of Targeted Testing:

• Regulatory Compliance: Labs measure PFAS levels against established regulatory thresholds set by agencies like the EPA, European Chemicals Agency (ECHA), and state regulatory bodies.
• High Sensitivity & Precision: Uses advanced analytical techniques such as LC-MS/MS for accurate quantification of known compounds.
• Standardized Methods: Laboratories adhere to guidelines like EPA Method 537.1 and EPA Method 533 for drinking water and environmental samples.
• Fast Turnaround: Because it focuses on a predefined list of compounds, targeted testing is highly efficient and streamlined, making it suitable for routine monitoring.
• Reproducibility: Standardized protocols ensure that results can be consistently replicated across different laboratories, supporting data reliability in regulatory reporting.

Limitations of Targeted Testing:

While targeted analysis is essential for compliance and routine environmental monitoring, it has a critical limitation—it only detects compounds that are already on a regulatory list. With over 12,000 known PFAS compounds, targeted methods account for only 1-2% of the total PFAS universe, leaving thousands of potentially harmful, unregulated chemicals undetected. This gap in detection underscores the need for non-targeted analysis to identify emerging threats.

The Role of Non-Targeted Testing for Emerging PFAS

A study conducted in Norway analyzed human exposure to both known PFAS and unrecognized fluorinated chemicals over a 2–3 week period. Using methods capable of detecting 64 PFAS compounds and extractable organofluorine (EOF), researchers found that up to 81% of detected fluorinated chemicals were previously unrecognized, with a median of 38%. Additionally, 36% of participants exhibited EOF concentration changes greater than 25%, suggesting ongoing exposure to unknown fluorinated compounds.

While targeted testing focuses on known PFAS contaminants, non-targeted testing takes a broader, exploratory approach. It is particularly useful for detecting previously unknown or unregulated PFAS compounds, making it indispensable for environmental surveillance, research, and regulatory advancements.

Key Features of Non-Targeted Testing:

• Detection of Unknown PFAS: Identifies unregulated or previously undiscovered PFAS compounds that are not included in targeted lists.
• Broad-Spectrum Screening: Uses high-resolution mass spectrometry (HRMS) to scan for a wide range of chemical signatures, allowing for the detection of novel PFAS.
• Future-Proofing: Non-targeted data can be revisited and reanalyzed as new PFAS compounds are identified in future research, ensuring laboratories stay ahead of regulatory developments.
• Environmental Surveillance: Plays a critical role in tracking emerging contaminants in air, water, and soil before formal regulatory standards are established. 

Comparison of Targeted vs. Non-Targeted PFAS Analysis

Both targeted and non-targeted PFAS testing are essential for a comprehensive contamination assessment. While targeted analysis ensures regulatory compliance and standardized reporting, non-targeted analysis is critical for uncovering the next generation of PFAS threats.

The Future of PFAS Testing: Automation & Compliance

As regulatory bodies like the EPA, FDA, and USGS continue to refine PFAS guidelines, laboratories will need to increase testing throughput and efficiency. Automation will play a critical role in streamlining sample preparation, data analysis, and reporting to handle the rising volume of PFAS testing demands.

The Role of Environmental LIMS Software in Closing the PFAS Mass Balance Gap

With current analytical testing covering less than 1-2% of known PFAS, laboratories need robust data management systems to bridge this detection gap. An environmental LIMS plays a pivotal role in enhancing testing efficiency, compliance, and comprehensive PFAS identification through both targeted and non-targeted workflows.

Key Contributions of an Environmental LIMS:

• Automated Data Management: Captures, organizes, and processes large volumes of PFAS testing data, reducing manual errors and improving traceability.
• Regulatory Compliance: Ensures adherence to EPA Methods 537.1, 533, and 1633 by defining sample processing and testing workflows, thereby maintaining accurate, audit-ready records for evolving PFAS regulations.
• Sample Tracking & Chain of Custody: Provides full traceability from collection to analysis, preventing contamination risks and ensuring data integrity.
• Integration with Advanced Instrumentation: Seamlessly connects with LC-MS/MS and HRMS systems, enabling laboratories to conduct both targeted and non-targeted PFAS testing for broader contaminant detection.

By automating workflows and enhancing analytical capabilities, an environmental LIMS enables laboratories to detect a wider range of PFAS compounds, ultimately helping to bridge the PFAS mass balance gap and advance environmental safety.

Conclusion: A Two-Pronged Approach for PFAS Detection

Effective PFAS analysis requires a dual approach—targeted testing ensures regulatory compliance, while non-targeted testing identifies emerging threats. By leveraging mass spectrometry, chromatography, and automation, laboratories can stay ahead of evolving regulations and safeguard public health.

As PFAS research advances, integrating both targeted and non-targeted workflows will be key to ensuring a cleaner, safer environment for future generations. Laboratories that adopt advanced detection methods and flexible testing strategies will be better positioned to tackle the growing challenge of PFAS contamination, ultimately contributing to stronger public health protections and environmental sustainability.