PFAS analysis has developed into a multi-method analytical field built around several distinct classes of analytical instruments. There is no single universal approach to PFAS analysis; current workflows combine different techniques, each designed for a specific analytical task. This reflects both the chemical diversity of PFAS and the growing range of questions laboratories are expected to answer.
Targeted LC–MS/MS for Quantitative Analysis
Routine quantitative PFAS analysis is typically performed using liquid chromatography coupled with tandem mass spectrometry on triple quadrupole LC–MS/MS systems operated in multiple reaction monitoring mode. The workflow is built for compound-specific quantification at trace concentration levels, with isotope-labeled internal standards supporting accuracy and reproducibility.
LC–MS/MS methods for PFAS are highly sensitive to matrix effects and background contamination. PFAS may originate from solvents, laboratory air, tubing, seals, or other instrument components. Contamination control and PFAS-adapted LC–MS/MS configurations therefore become part of method performance, not a secondary consideration.
GC–MS for Volatile PFAS and Precursors
Gas chromatography–mass spectrometry is applied to a narrower subset of PFAS, primarily volatile or semi-volatile compounds and selected precursor substances. When suitable derivatization strategies are used, GC–MS provides robust chromatographic separation and established mass spectral interpretation.
Compared to LC-based methods, the chemical scope of GC–MS is limited. In most PFAS workflows, it serves as a complementary tool aimed at specific compound classes rather than broad screening or routine monitoring.
Combustion Ion Chromatography for Total Fluorine Approaches
Combustion ion chromatography addresses questions that compound-specific methods cannot. In combustion-based workflows, organic fluorine present in a sample is converted into inorganic fluoride through thermal oxidation, which is then quantified by ion chromatography.
Combustion IC does not deliver molecular or structural information on individual PFAS. Instead, it is used to determine total or extractable organic fluorine, supporting screening studies, fluorine mass balance assessments, and evaluation of fluorinated fractions not captured by targeted LC–MS/MS analysis.
High-Resolution Mass Spectrometry for Screening
High-resolution mass spectrometry is used for suspect and non-target screening in PFAS analysis. In practice, this means accurate-mass instruments capable of high resolving power, typically based on time-of-flight or Orbitrap analyzers.
Unlike triple quadrupole LC–MS/MS systems, HRMS workflows are not limited to predefined analyte lists. They enable accurate-mass measurements, feature detection, and retrospective data analysis, and are typically implemented as full-scan–based workflows. The trade-off is that results are primarily qualitative or semi-quantitative and do not replace targeted LC–MS/MS for routine quantitative reporting.
Isotopologue-Based IRMS Approaches for Source Attribution
Isotopologue-based approaches apply isotope ratio concepts to intact PFAS molecules, enabling compound-specific isotopic characterization without complete molecular conversion. By resolving molecular isotopic patterns, these methods allow differentiation of PFAS originating from different production processes or sources.
The analytical focus is on relative isotopic composition rather than concentration. Such data support source attribution and environmental forensics and extend PFAS analysis beyond concentration-based measurements. These approaches remain technically demanding and are currently applied mainly in research settings.
Sample Preparation as a Method-Independent Requirement
Sample preparation is a critical step across PFAS analytical methods. For aqueous samples, solid-phase extraction is commonly used to achieve preconcentration and partial cleanup prior to LC–MS/MS or HRMS analysis. Sorbent selection, cartridge materials, and elution conditions directly influence recovery, matrix effects, and background contamination.
Solid and complex matrices such as soil, sludge, or biological samples require more extensive preparation, including solvent extraction, digestion, or combined mechanical and chemical treatment. These steps introduce additional variability and must be aligned with the selected analytical technique, including combustion-based workflows.
On-Site Sensors and Screening Tools
In parallel with laboratory-based methods, sensor-based and field-deployable tools are being developed to indicate the presence of PFAS directly on site. These devices provide rapid, qualitative or semi-quantitative information and are intended to support sampling strategies rather than replace laboratory analysis.
Selecting Instruments for the Question at Hand
PFAS analysis is defined by matching an analytical question to the instrument class that can answer it. A system that performs well for one task (routine quantification, broad screening, fluorine mass balance, or source-oriented studies) will not automatically perform equally well for another. Choosing instrumentation by reputation or sensitivity alone can lead to gaps in coverage, misfit data, or unnecessary complexity.
Effective PFAS work therefore depends on selecting methods with a clear understanding of what each instrument is designed to deliver, and where its limits begin.