MSUM: Solution for Extractables & Leachables Analysis - Instruments, Software, Database/Spectral Library

Importance of the Topic

Extractable and leachable (E&L) analysis is essential to safeguard product quality and patient or consumer safety across pharmaceutical, biopharmaceutical, medical device, food contact and consumer electronics industries. Accurate identification and quantitation of chemical impurities migrating from packaging or processing materials are critical to demonstrate regulatory compliance and minimize health risks.

Aims and Study Overview

This article reviews Thermo Fisher Scientific’s end-to-end solution for E&L analysis. It outlines multi-modal instrumentation, data processing software, spectral and mass-list databases, and standardized workflows designed to support early-stage extractables profiling, leachables testing and regulatory submissions.

Methodology

The workflow integrates complementary analytical techniques:

• Gas chromatography–mass spectrometry (GC-MS, GC-HRMS, headspace, EI/CI) for volatile and semi-volatile compounds.
• Liquid chromatography–high resolution mass spectrometry (LC-HRMS, LC-MS/MS, ESI/APCI) for non-volatile organics.
• Inductively coupled plasma techniques (ICP-MS, ICP-OES) for elemental impurities.

Instrumentation Employed

• TRACE 1310 GC, TSQ 8000 Evo and Q Exactive GC Orbitrap GC-MS/MS
• Vanquish UHPLC and Q Exactive Plus/Focus LC-Orbitrap MS
• Orbitrap Fusion Lumos Tribrid MS for ultra-high resolution and MSn capability
• iCAP Q and RQ ICP-MS, iCAP 7000 Plus ICP-OES
• ASE and IR spectrometers for material characterization

Main Results and Discussion

High resolution accurate mass (HRAM) data enable baseline separation of isobaric interferences and fine isotope structure analysis, improving elemental composition assignment and structure elucidation. Case studies include the identification of Irgafos 168 oxidation products, tinuvin and octabenzone quantitation with sub-ppb sensitivity, and unknown E&L component discovery in single-use bioprocess systems. The Compound Discoverer™ software streamlines component detection, adduct grouping, parallel database searching (mzVault, mzCloud, E&L mass lists), structure proposal, FISh scoring and differential lot-to-lot comparison.

Benefits and Practical Applications

• Comprehensive coverage of volatile, semi-volatile, non-volatile organic and elemental impurities.
• Robust workflows from early extractables screening to leachables qualification.
• Regulatory alignment with FDA, EMA, ICH, USP and ISO guidelines.
• Enhanced confidence in unknown identification via ultra-high resolution and MSn fragmentation.
• Time-saving data processing and reporting through integrated software and searchable databases.

Future Trends and Applications

Advances in orbitrap and tribrid mass spectrometry will drive routine million-resolution acquisition and deeper isotope structure insights. Cloud-based spectral libraries and AI-assisted de novo structure prediction will accelerate unknown characterization. Greater automation in sample extraction, data processing and compliance reporting is expected, as well as expansion of E&L mass lists to include novel additive degradants and next-generation packaging materials.

Conclusion

An integrated platform combining high-performance instrumentation, curated spectral and mass-list databases, and advanced software enables efficient, reliable E&L analysis. This approach supports safe product development, regulatory approval and ongoing quality control across diverse industries.

Reference

• FDA Container Closure Systems for Packaging Human Drugs and Biologics (May 1999)
• EMA Guideline on Plastic Primary Packaging of Medicinal Products (EMEA/205/04)
• ICH Q6A/B Test Procedures and Acceptance Criteria; Q8 Pharmaceutical Development
• USP Chapters 1663, 1664, 1665 on Extractables and Leachables
• ISO 10993 series for medical device biocompatibility