Regulations for per- and polyfluoroalkyl substances (PFAS) are rapidly tightening globally due to growing concerns over their persistence and health impacts. However, oversight is lagging in the pharmaceutical and medical device sectors, where patient safety is of paramount importance. This gap presents an immediate need for scientific leadership to establish new best practices.
This article, based on the Thermo Fisher Scientific webinar, “Comprehensive PFAS Screening in Pharmaceutical Packaging and Medical Devices”, features insights from Chongming Liu, Maciej Bromirski, and Jon Bardsley. The discussion centers on moving beyond the regulatory vacuum to define next-generation PFAS detection in extractables and leachables (E&L) testing.
The Analytical Challenge of Trace PFAS
PFAS analysis presents unique difficulties, even for experienced analytical scientists. The strong carbon-fluorine bonds are the source of their extreme chemical stability, making them difficult to degrade and challenging to measure at trace levels.
“PFAS are everywhere—even in labware and tubing—which makes background contamination one of the biggest analytical hurdles,” notes Bardsley, Market Development Manager at Thermo Fisher Scientific. “Without careful system design, you can easily end up measuring your own equipment rather than your sample.”
Traditional approaches, which use liquid chromatography coupled with mass spectrometry (LC-MS), often face key limitations in the following areas:
- Limited scope: They typically focus only on a small, targeted panel of known PFAS compounds.
- Sensitivity gaps: They struggle to reliably quantify compounds at sub-parts-per-billion (sub-ppb) levels required by modern safety limits.
- Methodology conflicts: Existing methods often rely on solid-phase extraction (SPE), which can inadvertently complicate or exclude the analysis of non-targeted PFAS, thereby failing to provide a comprehensive E&L profile.
Accurate and reliable data is crucial, especially when dealing with contamination and evolving standards. “Sensitivity is critical, but reliability is what gives the data real meaning,” emphasizes Bromirski, Senior Product Marketing Manager at Thermo Fisher.
A Single-Injection, Three-Fold Solution
To overcome these obstacles, a collaborative team of experts from Thermo Fisher and SGS Health Science developed a streamlined and robust liquid chromatography-high resolution accurate mass spectrometry (LC-HRAM-MS) workflow designed to maximize the data return from a single sample injection. This innovative approach utilizes a high-resolution mass spectrometer equipped with a high-field Orbitrap analyzer, capable of achieving a resolving power of 120,000 (at m/z 200).
The key feature of this workflow is the dual-mode, rapid polarity switching protocol. This allows the mass spectrometer to concurrently detect two chemically distinct groups of compounds—fluorinated and non-fluorinated—using electrospray ionization (ESI) negative mode for acidic PFAS compounds and ESI positive mode for most organic E&L compounds.
By operating in this integrated fashion, the system simultaneously achieves three complementary objectives:
Targeted quantitation of known PFAS: Quantifying a panel of common PFAS compounds down to sub-ppb levels (ESI negative mode).
Non-targeted discovery of unknown PFAS: Structural characterization of previously undetected fluorinated compounds using the highly precise, high-resolution accurate mass (HRAM) data and confirmation via data-dependent MS/MS fragmentation.
Simultaneous screening of non-fluorinated E&L: Comprehensive profiling of common extractable compounds (for example, plasticizers and stabilizers) alongside PFAS compounds (ESI positive mode).
This integrated approach represents a significant leap in analytical efficiency and confidence, providing a far more complete risk assessment in a single run.
Instrument Design for Low Background
A crucial element of the method is the use of a proprietary PFAS analysis kit and an innovative delay column. This kit replaces system components known to leach PFAS, while the delay column successfully separates ubiquitous background PFAS peaks from genuine sample peaks, effectively minimizing false positives and ensuring accurate quantitation.
Method optimization studies were performed, successfully increasing the short-chain PFAS response by up to 600% by adjusting source parameters (for example, lowering the spray voltage and temperature) from their default settings.
This optimized system design ensures the necessary precision to maintain the broader E&L capabilities researchers depend on.
Performance Results from Real-World Materials
The method's performance was validated by analyzing extracts from fluorinated ethylene propylene (FEP) materials, commonly used in pharmaceutical tubing and container systems. The data confirmed the viability of the three-fold detection strategy:
- Achieved low LOQs: Quantitation limits as low as 0.1 ppb for PFOA and sub-ppb limits for most other targeted compounds were demonstrated, satisfying stringent regulatory benchmarks.
- Expanded discovery: The single-injection non-targeted acquisition successfully identified and structurally proposed an additional five non-targeted PFAS compounds beyond the standard list, providing a wider risk profile.
- Confirmed trace exposure: Analysis confirmed that FEP materials can release multiple PFAS compounds at sub-ppb concentrations.
- Dual analytical benefit: The optimized system notably enhanced the overall E&L profile by substantially improving the quantitation of non-fluorinated extractables through separation from system background peaks.
Ultimately, these results validate the method's unique ability to deliver low-level, comprehensive data critical for informed risk assessment.
“Our data confirm that even commonly used fluoropolymer materials, like FEP tubing and bottles, can release trace PFAS,” notes Liu, Supervisor of E&L at SGS. “Detecting them at sub-ppb levels provides essential insight for risk assessment in packaging and device components.”
From Innovation to Preparedness
The significance of this work extends beyond analytical performance. For manufacturers, the ability to predict and mitigate risk offers not just compliance but the peace of mind that comes with a robust safety profile. This proactive stance is essential as similar standards are expected to expand into the pharmaceutical and medical device sectors.
By proactively adopting this comprehensive, low-background PFAS screening into existing E&L workflows, manufacturers shift from a reactive to a resilient quality system, minimizing regulatory risk.
“The regulatory environment is catching up fast,” notes Bardsley. “Developing robust, validated PFAS methods today means you’ll be ready when oversight expands tomorrow.”
Key Takeaways
For pharmaceutical laboratories managing E&L and trace contamination, these are the critical takeaways from the method development:
- Innovation leads regulation: The analytical framework developed in this study provides a forward-looking model capable of adapting to emerging PFAS standards.
- The power of integration: A single LC-HRAM-MS method achieves targeted quantitation, non-targeted PFAS discovery, and simultaneous non-fluorinated E&L screening.
- Trace detection is possible: Optimized instrument design and advanced background reduction methods successfully enable reliable, accurate detection down to sub-ppb levels, providing essential safety data.
“Innovation can lead to regulation,” summarizes Liu. The necessary tools to ensure PFAS safety and compliance are in place—it’s time to put them to use.