Simultaneous Targeted and Non-targeted PFAS Screening as Part of the Extractables Analysis of Pharmaceutical Container Closure, Manufacturing Components and Medical Device Materials by LC-HRMS

Per- and polyfluoroalkyl substances (PFAS) are known for their persistence in the environment and in the human body, leading to potential health issues. Regulatory agencies like the FDA and EPA have set stringent guidelines and limits for PFAS in various products and matrices, such as new PFAS National Primary Drinking Water Regulation, setting a Maximum Contaminant Level for nine different PFAS. However, there is still no regulatory guidance on PFAS levels present in pharmaceutical products and medical devices, which could compromise product safety and efficacy for drug products. As such, medical device and pharmaceutical companies should be proactive by staying up to date with current and future regulation, and develop risk mitigation strategies to avoid costly product recall or delays in approvals. To that end, having the ability to detect and quantitate PFAS in various pharmaceutical packaging and medical device materials is essential.

In this presentation, we report an LC-HRMS based concurrent targeted and untargeted detection of PFAS that could be extracted from manufacturing components and containers as part of extractables screening. Sensitive detection of multiple PFAS of interest at sub-ppb levels could be established using Full Scan data from an Orbitrap system, while collecting data dependent MS2 data for unknown identification of potential PFAS compounds within the same injection. In a case study, targeted PFAS could be detected at sub-ppb levels from Fluorinated Ethylene Propylene (FEP) bottles and tubing, and additional PFAS were revealed from the non-targeted analysis following common E&L practices.