Thermo Scientific Extractables & Leachables Workflow

Significance of the Topic

The safety of food and pharmaceutical products depends critically on the analysis of extractables and leachables from materials that come into contact with the product. Migration of volatiles, semi-volatiles, non-volatiles, and elemental impurities can pose health risks or impact product quality. Regulatory bodies worldwide require comprehensive unknown screening to ensure consumer safety and compliance.

Objectives and Study Overview

This whitepaper presents an integrated workflow for the identification, quantification, and confirmation of unknown impurities in contact-closure and food-contact materials. The goals are to:

• Detect a broad range of chemical species—from low-molecular-weight volatiles to high-molecular-weight non-volatiles and metals.
• Automate sample preparation and analysis to reduce turnaround time and cost.
• Ensure compliance with global regulations (e.g., US FDA, EU 10/2011, ICH Q3D, USP Chapters).

Methodology

The workflow is organized by analyte volatility and properties:

• Volatile organics: Headspace sampling and GC-MS analysis for rapid screening of low-molecular-weight compounds under USP headspace protocols.
• Semi-volatiles: Liquid extraction (with derivatization where needed) combined with GC-Orbitrap HRAM MS/MS for high-resolution accurate-mass identification and quantification.
• Non-volatiles: UHPLC separation with full-scan HRAM detection (Orbitrap), multi-mode ionization (ESI, APCI) and MSn for structural elucidation using spectral libraries.
• Elemental impurities: ICP-MS analysis following ICH Q3D and USP 232/233 guidelines, with automated dilution and compliance-driven software control.
• Accelerated solvent extraction (ASE) replaces traditional Soxhlet methods to reduce solvent volume and extraction time.

Used Instrumentation

The following instruments and software modules support the workflow:

• Thermo Scientific™ TriPlus™ 300 Headspace Autosampler
• Thermo Scientific™ ISQ™ Series Quadrupole GC-MS
• Thermo Scientific™ Q Exactive™ GC Orbitrap™ GC-MS/MS
• Thermo Scientific™ Vanquish™ UHPLC
• Thermo Scientific™ Q Exactive™ Series Hybrid Quadrupole-Orbitrap Mass Spectrometer
• Thermo Scientific™ iCAP™ RQ ICP-MS
• Thermo Scientific™ Dionex™ ASE™ 350 Accelerated Solvent Extractor
• Chromeleon™ CDS, TraceFinder™, Compound Discoverer™, Qtegra™ ISDS software

Main Results and Discussion

Automating headspace and ASE sample preparation reduced hands-on time by over 50% and solvent usage by up to 80%. High-resolution Orbitrap detection delivered mass accuracy below 1 ppm, enabling confident unknown identification and quantification over six orders of magnitude. Combining UHPLC, GC-MS, and ICP-MS generated comprehensive impurity profiles, meeting regulatory thresholds and ensuring reliable structural elucidation even in complex mixtures.

Benefits and Practical Applications

The presented workflow provides:

• Regulatory compliance for food contact and pharmaceutical packaging materials.
• Accelerated turnaround and lower cost per analysis through automation.
• Broad chemical coverage, from volatiles to high-molecular-weight compounds and metals.
• Robust structural identification using high-resolution accurate-mass data and cloud-based spectral libraries.

Future Trends and Opportunities

Emerging directions include integration of artificial intelligence for pattern recognition, expansion of cloud-based HRAM libraries, further miniaturization and green extraction techniques, real-time leachables monitoring, and fully digitalized workflows for end-to-end traceability.

Conclusion

This integrated extractables and leachables workflow leverages advanced automation and high-resolution instrumentation to deliver fast, accurate, and compliant impurity profiling. It addresses the full volatility spectrum and elemental analysis needs, ensuring product safety and regulatory adherence across industries.

Reference

1. US FDA 21 CFR 174–190
2. EU Regulation 10/2011 on food contact materials
3. USP Chapters 1633 & 1634 on packaging extractables
4. PQRI and BPOG guidelines for extractables and leachables
5. ICH Q3D Guideline for elemental impurities
6. USP Chapters 232, 233 & 2232 on elemental impurities