PFAS Sample Preparation Guide by Matrix and Method

Abstract

Reliable characterization of PFAS requires workflows designed to suit the specific properties of air, water, solids, biological materials, and food systems. This article outlines proven strategies for handling each matrix, including container choice, storage conditions, extraction paths, cleanup sequences, and confirmation steps that minimize artifacts. Guidance is provided for selecting SPE formats, managing matrix effects, and integrating carbon, mixed-mode, or dispersive approaches where needed. Common pitfalls and corrective actions are detailed for improved recoveries and precision. The discussion also maps these practices to major regulatory programs, enabling consistent preparation for both targeted quantification and broader screening efforts.

Section Overview

• Matrix at a Glance (Containers, Storage, Baseline Extraction/Cleanup)
• Workflows by Matrix
• Common SPE Prep Essentials
• Pitfalls & Fixes (By Matrix)
• Sample Preparation in Regulatory Methods
• Related Products

At a Glance

• Contamination control: Avoid contamination at ng/L–pg/g levels by using PFAS-free materials, performing routine blanks, and documenting all handling procedures.^11,1
• Matrix-specific workflows: Apply extraction and cleanup methods tailored to the sample matrix to maintain recovery and minimize matrix effects.^1,2,7
• Regulatory alignment: Follow prescribed workflows to ensure compliance with regulatory methods.^1–10

Matrix at a Glance (Containers, Storage, Baseline Extraction/Cleanup)

• Air and emissions: Collect samples using quartz or glass fiber filters with polyurethane foam (PUF) or XAD sorbents, either in passive or high-volume configurations. Store samples at low temperature. Extract filters and sorbent materials separately, combine extracts, concentrate, and analyze by LC–MS/MS for semi-volatile or polar PFAS, or by GC–MS for volatile compounds according to method scope.⁵
• Aqueous matrices (drinking water, surface water, groundwater, wastewater, leachate): Use PFAS-aware polypropylene (PP) or high-density polyethylene (HDPE) containers. Store at or below 6 °C. Enrich samples using solid-phase extraction (SPE) with WAX or HLB cartridges. Apply carbon cleanup for complex matrices, concentrate the extract, and analyze by LC–MS/MS. Direct injection may be used for non-potable water screening in Method 8327.^1,4,7
• Abiotic solids, sediments, and biosolids: Homogenize samples and store cold or frozen. Extract using pressurized liquid extraction (PLE), Soxhlet extraction, or supported liquid extraction (SLE). Apply carbon and SPE cleanup as needed, then concentrate and analyze by LC–MS/MS.^2,8
• Biological matrices (serum, plasma, tissues, milk): Perform protein precipitation or alkaline digestion followed by SPE (HLB or WAX) or online SPE. Apply lipid cleanup for tissue samples, concentrate, and analyze by LC–MS/MS.²
• Food, packaging, and migration studies: Extract using acetonitrile with acid, apply modified QuEChERS or dispersive SPE, and include an additional SPE step if required. Concentrate and analyze by LC–MS/MS.⁶

Workflows by Matrix

Air Samples

• The most frequently detected airborne PFAS include ionic and zwitterionic perfluoroalkyl acids (PFAAs) and neutral fluorotelomer alcohols (FTOHs), along with perfluoroalkane sulfonamido ethanols (FASEs) and perfluoroalkane sulfonamides (FASAs).⁵
• Collection: Use passive samplers such as PUF or SIP disks (with or without XAD) or active high-volume samplers with quartz or glass fiber filters and PUF/XAD in series. Bake filters at approximately 450 °C before use. Include field and trip blanks.
• Storage: Wrap samplers in aluminum foil or store in polypropylene; maintain at −20 °C.
• Extraction: Perform Soxhlet or accelerated solvent extraction (ASE) for PUF/XAD using methanol or methanol/dichloromethane mixtures. Extract filters separately with methanol or acetonitrile and combine all extracts.
• Cleanup/analysis: Use dispersive SPE as needed. Analyze ionic PFAS by LC–MS/MS and volatile precursors such as FTOHs by GC–MS.

Aqueous Samples

• Per- and polyfluoroalkyl substances (PFAS) have been widely detected across the aquatic continuum, encompassing drinking water, surface water, groundwater, wastewater, snowmelt, landfill leachate, and marine environments.^1,4
• Collection and storage: Use PFAS-free PP or HDPE containers at or below 6°C. Preserve as required by the method (e.g., with Trizma buffer for specific drinking water workflows).
• Extraction: Apply SPE (WAX,  Supel™ Swift HLB or HLB). Rinse and dry cartridges, elute with methanol containing ammonium hydroxide, concentrate, and reconstitute for LC–MS/MS analysis. Use ENVI-Carb for high dissolved organic carbon (DOC) matrices.
• Alternatives: Direct injection LC–MS/MS can be used for non-potable water screening with proper dilution and robust matrix tolerance.

Notes: Mixed-mode or HILIC columns may be necessary for short- or ultrashort-chain PFAS. Confirm LOQs to ensure adequate sensitivity.

Abiotic Solid Matrix Samples

Research on PFAS in abiotic solid matrices—including dust, soil, and sediments—primarily aims at the quantitative identification of a broad spectrum of compounds while continuously optimizing extraction and cleanup protocols to address emerging PFAS classes.^2,8

• Pretreatment: Record sample moisture, homogenize or sieve, and store at 4°C or frozen.
• Extraction: Perform Soxhlet, PLE, or SLE extraction, using basic conditions to improve recovery of anionic PFAS when appropriate.
• Cleanup: Use a combination of ENVI-Carb and WAX/HLB tandem cleanup. Include an additional ENVI-Carb step for sludge samples.

Notes: Consider zwitterionic and cationic PFAS and validate recoveries using suitable surrogate standards.

Biological Samples

The most extensively studied biological matrices for PFAS analysis include plasma, serum, and breast milk, while emerging research increasingly targets urine, hair, and nails for human biomonitoring, as well as wildlife tissues to inform environmental chemical management.²

• Pretreatment: Homogenize, then perform protein precipitation (using methanol or acetonitrile) or alkaline digestion. Follow with liquid-liquid extraction or SPE (HLB/WAX). Apply lipid cleanup for tissues.
• Throughput: Consider online SPE for serum or plasma and ASE or FUSLE for tissues when applicable.

Notes: Use isotope dilution and matrix-matched calibration or standard addition to correct for matrix effects.

Common SPE Prep Essentials^1,7

• Conditioning: Sequentially condition with methanol, then water, and buffer if required.
• Loading: Apply sample volumes appropriate for the matrix and monitor flow to prevent breakthrough.
• Rinsing and drying: Use mild aqueous rinses to remove matrix residues, and dry thoroughly under vacuum or nitrogen.
• Elution: Elute analytes using methanol containing approximately 0.1% ammonium hydroxide.
• Concentration and reconstitution: Evaporate gently under nitrogen and reconstitute in a compatible solvent before LC–MS/MS analysis.

Pitfalls & Fixes (By Matrix)

• Air: Residual PFAS on filters or PUF can interfere with results. Bake filters, pre-clean sorbents, always include field blanks, and combine filter and sorbent extracts.⁵
• Aqueous: Short-chain PFAS may break through during extraction. Use WAX or mixed-mode cartridges, verify recoveries, include ENVI-Carb for high-DOC matrices, and monitor for solvent or cap contamination.^1,4
• Solids and biosolids: Incomplete cleanup can cause signal interference. Use carbon and WAX/HLB cleanup in series, ensure thorough homogenization, and track moisture levels.^2,8
• Biological: Ion suppression from proteins and lipids can reduce accuracy. Perform thorough protein precipitation, apply isotope dilution, include lipid cleanup, and consider online SPE for improved throughput.²

Sample Preparation in Regulatory Methods

Discover More

• PFAS: Definition, Classification, Sources, Impact, & Detection
• PFAS Analysis Methods: Regulatory Alignment, QA/QC, and Contamination Control
• PFAS Column Selection for LC and GC

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