The Doctor Did Not Prescribe Irgafos: A Solution for Extractables and Leachables Analysis

Significance of the Topic

Extractables and leachables (E&L) analysis evaluates chemical compounds that can migrate from packaging or processing materials into drug, food or consumer products. This assessment is critical for safety and quality control across pharmaceuticals, medical devices, food contact materials and electronics.

Objectives and Study Overview

This study examines the oxidation of the polymer antioxidant Irgafos 168 under gamma irradiation and outlines a comprehensive E&L testing workflow. It highlights advanced sample preparation, multiple analytical platforms and data processing approaches to identify and quantify both volatile and non-volatile impurities.

Methodology

Automated accelerated solvent extraction (ASE) was compared to traditional Soxhlet extraction for efficiency and solvent use. Headspace sampling captured volatile organic compounds, while gas chromatography–mass spectrometry (GC-MS, GC–HRMS) profiled semi-volatiles. Liquid chromatography coupled to high-resolution accurate mass MS (LC-HRAM MS/MS) and charged aerosol detection (CAD) characterized non-volatiles. Inductively coupled plasma MS (ICP-MS/OES) determined elemental impurities.

Instrumentation Used

• Thermo Scientific ASE systems (ASE™ 350)
• TriPlus 300 Headspace Sampler and Trace 1310 GC with ISQ Series GC-MS and Q Exactive GC Orbitrap MS/MS
• Vanquish UHPLC with Q Exactive Plus Hybrid Quadrupole-Orbitrap MS and Vanquish CAD
• iCAP RQ and 7000 Plus ICP-MS/OES with Qtegra software
• Software: Chromeleon CDS, TraceFinder, Compound Discoverer, Mass Frontier, mzCloud/mzVault databases

Main Results and Discussion

ASE reduced extraction time from hours to minutes and solvent consumption by over 80% compared to Soxhlet while enhancing analyte recovery. Gamma irradiation of Irgafos 168 generated oxidized derivatives detectable by GC-HRMS with sub-fg sensitivity. Headspace-GC-MS enabled routine residual solvent analysis. LC-HRAM MS/MS with polarity switching captured a broad profile of non-volatile extractables and elucidated unknown structures using data-dependent fragmentation and substructure searches. CAD provided near-universal detection for compounds lacking UV chromophores.

Benefits and Practical Applications

This integrated workflow delivers comprehensive E&L profiling with high sensitivity, regulatory compliance (USP, ICH, ISO, ASTM, BPOG, BPSA standards) and streamlined data analysis. Automation minimizes operator error, accelerates time-to-result and supports risk assessments for product development and regulatory submissions.

Future Trends and Potential Applications

Advances in cloud-based spectral libraries, machine-learning algorithms for de novo structure elucidation and fully automated extraction-to-reporting pipelines will further enhance throughput and confidence in E&L studies. Expanding single-use systems in bioprocessing and evolving regulatory expectations will drive broader adoption of high-resolution multi-modal workflows.

Conclusion

A strategic combination of accelerated sample preparation, cutting-edge chromatography, high-resolution MS, universal detection and powerful data software provides an efficient solution for extractables and leachables analysis. This approach meets stringent safety and regulatory demands while optimizing laboratory resources.

References

• Fouyer K et al. Analytical Chemistry. 2012;84(20):8642–8649.