Vol. 7, Issue 2, Part F (2025)

The identification and control of volatile and semi-volatile extractable compounds originating from pharmaceutical packaging materials is paramount for drug safety and regulatory compliance.1 These compounds can potentially migrate into the drug product and compromise patient health. Conventional analytical methods are often challenged by the complexity of the volatile profiles released from polymeric packaging materials.2 This paper presents the development and validation of an optimized Headspace Gas Chromatography–Mass Spectrometry (GC-MS/HS) screening method.2 GC-MS is the established technique for volatile analysis, leveraging its high sensitivity and mass spectral library matching capabilities for the non-targeted identification of unknown extractables.4 The method is optimized using static headspace with high-temperature extraction suitable for packaging samples, followed by highly selective single-column chromatographic separation.1 Validation, executed according to ICH Q2(R1) guidelines 8, confirms the high specificity required to differentiate target extractables from matrix components, with expected accuracy (recovery) of 80.0%–120.0% and precision (%RSD) below 15%.9 This method establishes a robust and selective analytical tool for the comprehensive screening and analysis of volatile extractables in pharmaceutical packaging materials.