Thermo Scientific Extractables & Leachables Workflow

Importance of the topic

Extractables and leachables analysis is critical for ensuring the safety and compliance of materials that contact food, beverages, and pharmaceuticals. Unintended chemicals migrating from packaging or container-closure systems can pose health risks or compromise product quality. A systematic workflow for identifying, quantifying, and characterizing volatile, semi-volatile, non-volatile, and elemental impurities supports regulatory compliance and safeguards consumer health.

Objectives and overview of the workflow

The primary goal is to establish a robust, high-throughput analytical strategy for unknown impurity screening and quantification across diverse sample matrices. Key objectives include:

• Detection and identification of all suspect extractables and leachables in food contact materials (FCMs) and pharmaceutical container-closure systems.
• Compliance with global regulations (FDA 21 CFR, EU Regulation 10/2011, USP, PQRI, BPOG, ICH Q3D, USP 232/233).
• Minimizing analysis time and solvent usage while maximizing data confidence and throughput.

Methodology and instrumentation used

The workflow integrates a combination of solvent extraction, chromatographic separation, and mass spectrometric detection tailored to compound volatility and chemical class:

• Accelerated Solvent Extraction (ASE 350) replaces traditional Soxhlet, reducing extraction time (<0.5 h) and solvent consumption (<30 mL/sample).
• Headspace autosampling (TriPlus 300) coupled to GC-MS for volatile organics, employing ultraclean Chromacol vials and TraceGOLD GC columns.
• Automated derivatization and injection (TriPlus RSH Autosampler) with Orbitrap GC-MS (Q Exactive GC) for semi-volatile compound profiling, delivering <1 ppm mass accuracy and femtogram sensitivity.
• UHPLC separation (Vanquish UHPLC) combined with HRAM Orbitrap LC-MS/MS for non-volatiles, leveraging ESI/APCI dual ionization and advanced spectral libraries (mzCloud).
• ICP-MS (iCAP RQ) with Qtegra ISDS software for trace elemental impurities, featuring intelligent auto-dilution and FDA 21 CFR 11–ready compliance.

Main results and discussion

Implementation of this integrated workflow delivers:

• Comprehensive impurity coverage from light volatiles to high-molecular-weight non-volatiles and metals in a single laboratory platform.
• Enhanced sensitivity and selectivity through high-resolution accurate mass (HRAM) detection and full MS/MS capabilities for confident unknown identification.
• Significant reductions in sample preparation time and solvent consumption via automated extraction and autosampler modules.
• Streamlined data acquisition and processing using compliant chromatography and MS software (Chromeleon, TraceFinder, Compound Discoverer, Qtegra) ensuring audit trails and easy method validation.

Benefits and practical applications of the method

This end-to-end approach offers distinct advantages for QA/QC, regulatory submissions, and R&D in food and pharmaceutical industries:

• Rapid turnaround with automated workflows reduces manual intervention and labor burden.
• High confidence in identification and quantification supports risk assessment and safety evaluations.
• Flexible platform adapts to evolving regulatory guidelines and complex sample matrices.
• Data integration across multiple detection techniques enables cross-validation and comprehensive impurity profiling.

Future trends and applications

Emerging directions include:

• Cloud-based spectral libraries and AI-driven deconvolution to accelerate unknown identification.
• Integration of real-time monitoring sensors and microfluidic extraction for in-line leachables screening.
• Expansion of miniaturized, portable MS systems for on-site compliance testing.
• Advanced chemometric tools for predictive migration modeling and lifecycle risk management.

Conclusion

A comprehensive, automated extractables and leachables workflow leveraging advanced extraction, chromatography, and HRAM mass spectrometry offers robust compliance solutions. By uniting speed, sensitivity, and regulatory alignment, laboratories can confidently detect and quantify impurities across diverse materials, ensuring product safety and quality.

References

• FDA 21 CFR 174–190; EU Regulation 10/2011
• USP Chapters 232, 233; ICH Q3D
• PQRI and BPOG Extractables & Leachables Guidelines