Laboratories worldwide face mounting pressure to detect per- and polyfluoroalkyl substances (PFAS) across a broad range of sample types—from water and soil to food and pharmaceuticals. Detecting and quantifying these persistent pollutants typically requires multiple complex methods. Now, scientists at SCIEX and York University are collaborating to change that.
Their LC-MS/MS approach enables detection of ultra-short, short-, and long-chain PFAS compounds in a single injection. It offers a potential breakthrough for labs working to comply with emerging safety regulations from the U.S., EU, Canada, and beyond.
Analytical Barriers to the “Shorties”
Historically, ultra-short PFAS such as trifluoroacetic acid (TFA) were either ignored or underestimated. According to Craig Butt, Senior Manager, Scientific Marketing at SCIEX, the analytical difficulty led many researchers to dismiss these compounds altogether. “It was very polar, it didn’t accumulate, and it was hard to measure. So people stopped looking,” he advises.
Cora Young, Professor and the Roger Chair in Chemistry at York University, encountered these challenges firsthand. Her earlier research into short-chain PFAS used ion chromatography-mass spectrometry (IC-MS), not LC-MS/MS. LC-MS methods at the time couldn’t effectively handle matrix effects—even in clean samples such as ice cores. “We had to do extractions even when the concentrations were high enough to direct inject,” she recalls.
LC columns struggled to retain highly polar compounds, and contamination with TFA made quantification especially difficult. As a result, even when concentrations were significant, analysts couldn’t avoid sample prep—defeating the promise of simplicity in direct injection.
Chromatography Catches Up
SCIEX and York University tackled this issue from the chromatographic side. Improvements in reverse-phase LC allowed better separation of matrix interferences and more consistent retention, even for challenging analytes such as TFA.
“The novelty isn’t on the mass spec side,” notes Butt. “PFAS ionize extremely well because of their physical chemical properties. The challenge has always been on the chromatography side—getting good retention, managing matrix effects, and ensuring reproducibility.”
Background contamination also remains a persistent issue. “Analysts know PFAS is everywhere,” he explains. “But with TFA, it’s another order of magnitude.” Even delay columns—commonly used to separate system-related contamination—had to be redesigned. The extreme polarity of ultra-short PFAS meant existing solutions caused signal overlap and distorted peaks.
Environmental Signals and Exposure Trends
Young’s work has helped shine a spotlight on the widespread presence of ultra-short PFAS. Her ice core analyses, for instance, show clear temporal trends that link TFA spikes to the use of CFC replacements—chemicals introduced under the Montreal Protocol.
“Levels were substantially higher than any other PFAS we measured in ice cores,” she said. This was expected from an atmospheric perspective, but came as a surprise to many in the PFAS field.
TFA’s prevalence in rain, crops, and beverages has also raised new concerns. “Anything derived from plants—tea, wine, beer—you expect to find TFA, and we do,” warns Young. She adds that she'd be more surprised to find a sample without PFAS contamination than with it.
Exposure is no longer limited to industrial zones. PFAS now reach surface waters, agricultural soil, and food chains via atmospheric deposition and wastewater. “We’re starting to go upstream to look for contamination,” adds Butt, referencing growing interest in wastewater analysis and biosolid tracking.
Regulatory Lag and the Case for Method Consolidation
While Canada and the EU are moving toward class-based regulation that includes TFA, the U.S. EPA has yet to classify it within PFAS rules. Germany has begun looking at specific regulations for TFA, but most global guidance still focuses on legacy compounds.
This regulatory gap, combined with the analytical complexity, makes unified testing methods all the more critical. SCIEX’s approach offers one path forward by enabling labs to monitor both long-chain and ultra-short compounds with a single method. “With the method we’ve created, you can get everything in one injection rather than increasing your workload,” emphasizes Butt.
Most labs already rely on LC-MS/MS for PFAS testing, making the transition practical. “It’s accessible, and people have the expertise to use it,” asserts Young. IC-MS, by contrast, requires different skill sets and less common instrumentation.
The Road Ahead
As detection becomes easier and regulations expand, more labs will likely turn to LC-MS/MS to capture the full PFAS picture. Whether it’s in rainwater, wastewater, pharmaceuticals, or food and beverages, these persistent chemicals continue to surface—forcing scientists, regulators, and industries to keep up.
“It’s not good enough just to know your wine is contaminated,” Butt said. “You need to know why.”