Dynamic Headspace GC–MS to Obtain Defined Uncertainty Factors for Volatiles

The identification and quantification of volatile organic compounds (VOCs) from medical devices represents a critical safety concern since some VOCs are known carcinogens. Determining these extractables at or above the Analytical Evaluation Threshold (AET), as specified in ISO 10993-18:2020/Amd 1:2022, is necessary for evaluating their toxicological impact. One component within the AET equation includes the uncertainty factor (UF), designed to broaden the threshold to include extractables that exhibit lower response than the signal level upon which the AET relies. However, accurately quantifying these extractables poses challenges due to the variation in response factors (RF), impacting consistent identification at identical concentrations. This study aims to address this challenge by assessing the feasibility of an optimized dynamic headspace (DHS)-GC–MS method to produce defined uncertainty factors (UF) for volatiles. By utilizing a standard mixture of 76 volatile compounds the optimized DHS-GC–MS method demonstrated successful identification of over 90% of volatile compounds in the mixture within a concentration range of 0.04–80 ng mL⁻¹ for most tested compounds. An RF database was created using calibration curves generated for each of the compounds to obtain defined UFs. Two methods were explored to calculate the UF using the DHS method: average RF across all the compounds and the linear slope of the calibration curve. Our results provided defined UF values of 3–5 for both RF calculation methods validating the feasibility of using the DHS-GC–MS as a suitable alternative to detect and quantify volatiles detected in medical device extracts.