Comprehensive PFAS screening in pharmaceutical packaging and medical devices by LC-HRAM-MS

Importance of PFAS Screening in Pharmaceutical Packaging and Devices

Per- and polyfluoroalkyl substances (PFAS) are persistent chemicals with known health risks and regulatory focus. Pharmaceutical packaging and medical devices, often constructed from fluorinated polymers, may leach PFAS into drug products. A comprehensive screening strategy ensures patient safety, supports regulatory compliance, and mitigates risk of recalls.

Study Objectives and Overview

This work aimed to develop a single LC-HRAM-MS method combining targeted quantitation and non-targeted screening of PFAS in extracts of fluorinated ethylene propylene (FEP) bottle and tubing materials. Sensitivity to sub-ppb levels and rapid identification were key goals.

Methodology and Instrumentation

Samples were extracted per ISO 10993-12: bottle and tubing materials were incubated with 50% ethanol/water or isopropanol at controlled temperature and time. Extracts were analyzed by:

• Thermo Fisher Vanquish Horizon UHPLC equipped with a PFAS Analysis Kit and delay column to reduce background
• Orbitrap Exploris 120 mass spectrometer with heated electrospray ionization in polarity-switching mode
• Chromeleon CDS 7.3.2 for data acquisition and targeted quantitation
• Compound Discoverer 3.3 SP3 for non-targeted screening and spectral library matching

Main Results and Discussion

Targeted analysis of 17 PFAS achieved limits of quantitation between 0.1 and 1 ppb with linearity up to 500 ppb and ≥7 scans per peak. In FEP extracts, PFPeA, PFNA and PFUdA were quantified at sub-ppb levels. Non-targeted analysis identified additional PFAS, including pentafluoropropanoic acid and 2,2-difluoro-2-(trifluoromethoxy)acetic acid, some exceeding 1 ppb by surrogate quantitation. The delay column effectively separated system contaminants, improving confidence in sample-derived signals.

Benefits and Practical Applications

This single-injection workflow offers both targeted and broad-scope screening of PFAS and other extractables, with high sensitivity, minimal background interference, and 21 CFR Part 11 compliance. It supports risk assessment and quality control in pharmaceutical manufacturing.

Future Trends and Potential Applications

Emerging regulations will demand deeper PFAS coverage and lower detection limits. Expanding spectral libraries, employing AI-driven annotation, and extending the method to diverse polymeric materials and biologics containers will enhance extractables and leachables risk management.

Conclusion

The presented LC-HRAM-MS approach, leveraging advanced instrumentation and software, provides a robust, sensitive, and comprehensive solution for PFAS screening in pharmaceutical packaging. It ensures reliable detection, quantitation, and identification of targeted and unknown PFAS, supporting regulatory readiness and product safety.

Reference

• U.S. EPA PFAS National Primary Drinking Water Regulation, Federal Register, 2024.
• ISO 10993-12 Biological Evaluation of Medical Devices – Part 12: Sample Preparation and Reference Materials, 2021.
• USP <665> Plastic Components and Systems Used to Manufacture Pharmaceutical Drug Products and Biopharmaceutical Drug Substances and Products, USP-NF, 2022.
• BioPhorum Operations Group Best Practices Guide for Extractables Testing of Single-Use Components, 2020.
• Du J. et al. Generation of a Custom Spectral Library for Plant Oil-Based Additives Identification in Extractables and Leachables, Thermo Fisher Scientific AN1586, 2022.
• Lu J. et al. Extractable Analysis of Rubber Stoppers for Pharmaceutical Applications, Thermo Fisher Scientific AN419, 2021.
• Sanchez JM, Tautenhahn R. PFAS Non-Targeted Analysis Workflow by HRMS, Thermo Fisher Scientific AN1826, 2023.
• Getzinger GJ et al. In Silico Spectral Library for PFAS Suspect Screening, Anal Chem 2021, 93(7):2820-2827.
• Charbonnet JA et al. Communicating Confidence in PFAS Identification by HRMS, Environ Sci Technol Lett 2022, 9:473-481.