Thermo Scientific Extractables & Leachables Workflow

Importance of the topic

Extractables and leachables analysis is critical for ensuring the safety and compliance of pharmaceutical products and food contact materials. Migration studies detect unknown non-intentionally added substances that may compromise consumer health. Regulatory agencies mandate comprehensive profiling of volatile, semi-volatile, non-volatile organic compounds and elemental impurities across diverse polymeric materials.

Aims and study overview

The primary objective is to identify and quantify extractables under exaggerated laboratory conditions and leachables under normal use scenarios. This workflow covers volatiles, semi-volatiles, non-volatiles, and elemental impurities to meet global guidelines including USP, PQRI, BPOG, ICH Q3D, FDA 21 CFR, and EU 10/2011.

Methodology and instrumentation

• Headspace autosampling with Thermo Scientific Triplus 300 and HS-GC-MS (ISQ Series) for volatile organics.
• Liquid injection GC-MS with Q Exactive Orbitrap for semi-volatiles, delivering sub-ppm mass accuracy.
• UHPLC-HRAM analysis using Vanquish UHPLC and Q Exactive Orbitrap, complemented by Charged Aerosol Detection and cloud-based mzCloud library for non-volatile organics.
• ICP-MS (iCAP RQ) with Qtegra ISDS software for elemental impurities in compliance with USP Chapters 232/233 and ICH Q3D.
• Accelerated solvent extraction (Dionex ASE 350) for rapid, low-solvent sample preparation.

Main results and discussion

The integrated approach achieved high throughput and sensitivity from low-molecular-weight volatiles to high-mass non-volatiles and trace metals. Orbitrap MS provided accurate identification (<1 ppm mass error) and quantification across a wide dynamic range. Automation and advanced software platforms (Chromeleon, TraceFinder, Compound Discoverer) streamline data processing, ensure 21 CFR 11 compliance, and facilitate reporting.

Benefits and practical applications

• Significant reduction in analysis time and solvent consumption.
• Enhanced confidence in impurity identification and quantification.
• Full regulatory compliance across multiple jurisdictions.
• Comprehensive coverage of chemical classes and matrices.

Future trends and opportunities

Emerging developments include expanded cloud-based spectral libraries, machine learning for unknown profiling, further automation of extraction and analysis workflows, miniaturized sample preparation, and integration of real-time monitoring to accelerate safety assessments.

Conclusion

The described Thermo Scientific workflow combines state-of-the-art instrumentation and automation to deliver a robust, regulatory-compliant platform for the comprehensive analysis of extractables and leachables. Ongoing innovations will continue to enhance throughput, sensitivity, and confidence in impurity characterization.

References

• US FDA 21 CFR 174–190
• EU Regulation 10/2011
• USP Chapters 1633, 1634, 232, 233, 2232
• PQRI and BPOG Guidelines
• ICH Q3D