Analytical Solutions for Extractables, Leachables, and Migration Testing

Importance of the Topic

Contact materials such as plastics, rubbers, metals, and coatings can release extractable and leachable compounds into pharmaceuticals, foods, and cosmetics. Accurate characterization of these compounds is essential to ensure consumer safety, meet regulatory requirements, and prevent product recalls.

Objectives and Study Overview

This application note outlines a systematic, risk-based framework for extractables and leachables (E&L) testing. It aims to demonstrate analytical workflows that achieve high separation power, sensitive identification of unknowns, and streamlined data processing to support compliance documentation and accelerate time to market.

Methodology and Instrumentation

The approach integrates controlled solvent extractions, supercritical fluid extraction, and multiple chromatographic techniques coupled with high-resolution mass spectrometry and compliance-ready data systems. Key instrumentation includes:

• ACQUITY UPLC I-Class System for low-dispersion, high-resolution liquid chromatography
• APGC source coupled to Xevo G2-XS QTof for soft ionization and structural elucidation
• MV-10 ASFE Supercritical Fluid Extraction for rapid, selective sample preparation
• ACQUITY UPC2 SFC with Trefoil, Torus, and Viridis column chemistries for achiral and chiral separations
• Vion IMS-QTof for added ion mobility separation and collision cross-section confirmation
• UNIFI Scientific Information System for integrated data acquisition, processing, and reporting
• ACQUITY Arc dual-path chromatography system emulating HPLC and UHPLC methods
• Empower Chromatography Data Software for regulatory-compliant data management
• ACQUITY QDa Mass Detector for routine mass confirmation in QC workflows

Key Results and Discussion

Fast UPLC and APGC-MS workflows provided comprehensive detection of both polar and nonpolar extractables in polymeric packaging samples. Supercritical fluid extraction reduced solvent use and simplified sample cleanup. Ion mobility separation in Vion IMS-QTof offered an extra dimension for resolving coeluting compounds. The binary comparison feature in UNIFI facilitated differential analysis against blank extracts, highlighting trace contaminants.

Benefits and Practical Applications

• Maximized separation efficiency and sensitivity for complex matrices
• Enhanced structural information enabling identification of unknown degradation products
• Automated data handling and reporting to support audit readiness
• Reduced cycle times through integrated, green extraction methods
• Scalable workflows from R&D to routine QC release testing

Future Trends and Applications

Increasing adoption of single-use systems in biopharmaceutical production will drive demand for more sophisticated E&L testing. Green analytical techniques, such as supercritical fluid extraction and CO2-based SFC, will continue to grow. Advances in ion mobility, machine learning-driven data processing, and cloud-based informatics will further enhance throughput and regulatory compliance.

Conclusion

A comprehensive E&L testing strategy that combines advanced extraction, high-resolution separation, and integrated data management ensures product safety and regulatory compliance while improving laboratory efficiency.

References

No specific literature citations were provided in the source document.