PFAS Analysis Toolkit: LC/MS/MS, Total Oxidizable Precursors (TOPS) and Total Organic Fluorine (TOF)

Feb. 12 2021

"What’s the difference and when do i use one over the other?"

Over the past ten years, there has been an extraordinary amount of attention focused on perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA) and related per- and polyfluorinated alkyl substances (PFAS)1, particularly with respect to their characterization, delineation, management and regulation in the environment. Environmental stakeholders are continually developing a better understanding of: occurrence, exposure and toxicity; proper sampling and analysis protocols; and remedial options.

From a testing standpoint, PFAS analysis has been primarily through liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS). As a “targeted” analytical technique, the results are limited to a fixed set of parameters. In other words, the results do not provide a comprehensive measure of the magnitude of the total pool of PFAS that may exist in contaminated soils and water, nor does it measure the potential for targeted PFAS formation due to natural transformation of precursor compounds over time to the regulated, targeted end products.

In an attempt to identify the presence of other, non-target PFAS present in an impacted sample, the total oxidizable precursors (TOPs) assay was developed1. More recently, there has been a focus in the industry to develop and validate lower cost alternatives that also provide a more comprehensive measure of total PFAS impact. This has resulted in several methods for measuring total organic fluorine (TOF) as a proxy for total PFAS contamination.

Each of these analytical approaches offers distinct advantages for environmental practitioners. At the same time, the limitations of each need to be considered when assessing their utility in different situations.

The advantages and limitations of the various PFAS test methods are presented in Table 1.

Table 1: Advantages and Limitations of PFAS Test Methods

  • Characterization of individual PFAS
  • Target PFAS delineation
  • Risk Assessment
  • Regulatory Compliance
  • Provides accurate concentrations for individual PFAS
  • Typical parameter lists include 20-50 compounds
  • 1-2 ng/L reporting limits meets all current regulatory standards
  • Higher cost test
  • “Targeted analysis”, i.e., reports 30-40 individual compounds…out of a potential 5000+ PFAS
Total Oxidizable Precursors (TOPs) Assay
  • Indication of total PFAS contamination
  • PFAS (target and non-target) delineation
  • Risk Assessment
  • Regulatory Compliance
  • Future Liability
  • Provides accurate concentrations for individual PFAS
  • Indicates the presence of compounds not measured by PFAS by LC/MS/MS
  • Indicates potential for future liability due to transformation of precursor compounds
  • Labor intensive assay, leads to longer turnaround times
  • High cost
  • Not fully quantitative
  • High sample variability
  • Does not necessarily provide a “total” PFAS result
Total Organic Fluorine (TOF)
  • Measure of total PFAS contamination
  • Is my sample “PFAS-free?”
  • Complements existing approaches
  • Provides concentration of organic fluorine, which is representative of the presence or absence of PFAS
  • Less labor intensive
  • Lower priced analysis
  • Reporting limits 2 µg/L (total F) in water

“When do I use PFAS by LC/MS/MS, TOPs Assay and/or TOF by CIC?”

Regulatory Compliance
Site Characterization
Contaminant Delineation
Complete Remediation
Site Risk (Future Liability)  
PFAS-free Product (e.g. AFFF)    



The determination of individual, target PFAS is performed using isotope dilution and liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS). These analytical protocols represent industry accepted best practices and are typically based on United States Environmental Protection Agency (US EPA) methods.

Samples are spiked with isotopically labelled analogues of the native compounds being measured. Solid samples undergo an aqueous (methanol/water) extraction. Liquid samples or extracts from solid samples are submitted for solid phase extraction (SPE), clean-up and concentration. The resultant extracts are then analyzed by LC/MS/MS.


PFAS analyses using LC/MS/MS typically identify, quantify and report between 20-50 PFAS. However, it is well understood that there are potentially thousands of PFAS (5000+) present in the environment, most of which are unknown or uncharacterized. These are often referred to as ”dark matter”.

It has been shown2 that through biological processes precursor compounds within this PFAS dark matter can break down or transform into PFAS end products that are measured. By doing so, this dark matter can contribute toxicity risk beyond that identified by PFAS by LC/MS/MS.

Based on a published method1, the TOPs assay is an analytical approach developed to provide an indication of non-target PFAS by modelling the in situ behavior of the dark matter in the laboratory. In short, the TOPs assay provides an approach to accelerating and predicting in situ precursor behavior.

To summarize the method:

  • Samples are collected in duplicate
  • The first aliquot is analyzed for target PFAS using LC/MS/MS to establish current or baseline concentrations
  • The second aliquot is oxidized, transforming PFAS precursors to PFAS end products, and then analyzed by LC/MS/MS
  • The change in target PFAS concentration is representative of higher molecular weight PFAS (“precursors”) that may, over time, convert to the lower molecular weight PFAS end products


Total Organofluorine (TOF) analysis gives a quantitative assessment of both the same PFAS compounds that are currently reported by LC/MS/MS and other fluoroorganic compounds not readily determined by standard PFAS testing. It reports a cumulative single parameter for water samples in µg/L or soil samples in µg/kg rather than individual components.

The measurement of TOF in environmental matrices, among others (e.g. AFFF, consumer products, etc.) provides the user with single result that is representative of the total PFAS concentration in the sample. Considering organic fluorine as a proxy for PFAS, the concentration measured in a sample will be representative of total PFAS. The total PFAS concentration in the sample is approximated by dividing the TOF result by 65%; the proportion of organic fluorine in PFOS.

Sample extracts are prepared in a manner that removes inorganic fluorine compounds, leaving only organofluorine compounds, the majority of which will be PFAS. The extracts are then incinerated at high temperature (>1000° C), and the mineralized fluorine measured by ion chromatography.


[1] Houtz, E.F. and Sedlak, D.L. (2012), Environ. Sci. Technol., 46, 9342-9349

[2] Wang, et. al. (2005) Environ. Sci. Technol., 39, 7516-7528