PFAS Analysis by LC-MS/MS: Accurate Quantification of “Forever Chemicals” in Water, Food, and Environmental Matrices

Per- and polyfluoroalkyl substances (PFAS) represent a large class of synthetic fluorinated chemicals widely used in industrial, consumer, and firefighting applications due to their thermal stability, surfactant properties, and chemical inertness. However, these same properties render PFAS highly persistent in the environment, earning them the name “forever chemicals.”
Mounting evidence linking PFAS exposure to endocrine disruption, immunotoxicity, developmental effects, and carcinogenicity has led to stringent global regulations, including ultra-low detection limits in drinking water and food.
Liquid Chromatography coupled with Tandem Mass Spectrometry (LC-MS/MS) has emerged as the gold-standard analytical technique for PFAS determination due to its unmatched sensitivity, selectivity, and multi-analyte capability.
This technical blog outlines a science-driven LC-MS/MS workflow for PFAS analysis, supported by chromatographic interpretation and regulatory relevance.

Why PFAS Require LC-MS/MS Analysis

PFAS compounds are:

•   Highly polar
•   Thermally stable
•   Often present at ng/L (ppt) levels
•   Structurally similar across homologous series (C4–C14)

Conventional techniques (GC, UV, single-quad MS) are inadequate due to:

•   Lack of volatility
•   Poor chromophoric response
•   Extensive isobaric and matrix interference

LC-MS/MS using Multiple Reaction Monitoring (MRM) overcomes these challenges by providing:

•   Molecular specificity
•   Extremely low detection limits
•   Robust quantification across complex matrices

LC-MS/MS Method Overview

PFAS are separated using reverse-phase LC, typically employing fluorine-free columns and mobile phases to minimize background contamination.

Key method features

•   Negative electrospray ionization (ESI−)
•   Compound-specific MRM transitions
•   Isotopically labeled internal standards
•   Quantification at ppt to low-ppb levels

Target analytes typically include:

•   PFOS, PFOA
•   PFHxS, PFHxA
•   PFNA, PFDA
•   Emerging short-chain PFAS (GenX, PFBS)

Regulatory Relevance

LC-MS/MS PFAS analysis aligns with major global frameworks:

•   US EPA 537.1 / 533
•   EU Drinking Water Directive
•   ISO 21675
•   Food safety and environmental monitoring programs

Detection limits achieved are well below current and proposed regulatory thresholds.

Applications Across Sectors
Drinking & Ground Water

•   Compliance monitoring
•   Source identification
•   Treatment efficacy evaluation

Food & Packaging

•   Migration studies
•   Raw material screening
•   Import/export compliance

Environmental Monitoring

•   Soil and sediment assessment
•   Industrial discharge evaluation
•   Site remediation studies

R&D and Emerging PFAS

•   Short-chain PFAS
•   Replacement chemistries
•   Non-targeted screening (HRMS extension)

Conclusion

LC-MS/MS provides a robust, sensitive, and regulatorily aligned solution for PFAS determination across water, food, and environmental matrices. The combination of:

•   Optimized chromatography
•   MRM-based mass spectrometry
•   Isotopically labeled internal standards

ensures accurate quantification at trace levels, even in complex matrices.

As PFAS regulations continue to tighten globally, science-backed analytical capability becomes indispensable. This LC-MS/MS approach positions laboratories to meet present and future compliance demands with confidence.

Contributed by: Rituparna Mukherjee https://www.linkedin.com/in/rituparna-mukherjee-038b56224

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