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

Importance of the Topic

Extractables and leachables (E&L) analysis is critical to ensure safety and quality of pharmaceuticals, biopharmaceuticals, medical devices, food packaging and consumer products. Uncontrolled migration of chemical impurities from materials into products can compromise patient health, product efficacy and regulatory compliance. A comprehensive E&L strategy provides risk assessment of materials in contact with sensitive formulations, supports regulatory submissions and accelerates market approval.

Objectives and Study Overview

This white paper presents Thermo Fisher Scientific’s integrated solution for E&L studies. The goals are to describe:

• Key regulatory requirements and industry guidelines for E&L analysis
• Multi-platform instrumentation for profiling volatile, semi-volatile and nonvolatile impurities
• Advanced data processing software, databases and spectral libraries for confident identification, structural elucidation and quantitation

Methodology and Used Instrumentation

E&L analysis combines extraction protocols with orthogonal analytical techniques:

• GC-MS and GC-HRMS (TSQ 8000 Evo Triple Quadrupole, Q Exactive GC Orbitrap, ISQ Single Quadrupole) for volatile/semi-volatile compounds via split/splitless, headspace and SPME methods
• LC-MS/MS and LC-HRMS (Vanquish UHPLC coupled to Q Exactive Plus, Q Exactive Focus, Orbitrap Fusion Tribrid MS) using ESI/APCI ionization for polar and nonvolatile species
• Elemental analysis by ICP-MS/OES (iCAP 7000 Plus, iCAP Q, iCAP RQ) for residual metals

Data acquisition employs full-scan accurate mass, data-dependent MS2 with stepped collision energies and polarity switching. Quantitation is performed with high-resolution MS targeting key E&L markers.

Main Results and Discussion

High-resolution accurate mass (HRAM) measurements at up to 140 000 resolving power enable baseline separation of isobaric species and isotope fine structure. Case studies demonstrate:

• Identification of Irgafos 168 degradation products by combining full-scan positive/negative data with MS/MS spectra and FISh scoring
• Quantitation of model extractables (octabenzone, Tinuvin 328) with sub-ppb sensitivity and linear calibration across relevant ranges
• Untargeted screening of IV bag extracts, followed by database-driven compound discovery using mzVault and Compound Discoverer for both known and unknown species

Software tools such as TraceFinder, Compound Discoverer 2.1, Mass Frontier, mzCloud and mzVault streamline data processing, structure elucidation and result interpretation. Custom E&L compound lists support targeted screening while de novo workflows assist in novel impurity identification.

Benefits and Practical Applications

The integrated solution offers:

• Improved confidence in E&L identification through high mass accuracy, isotope fidelity and informative MSn data
• Regulatory readiness by aligning workflows with USP <1663>, <1664>, FDA, EMA, ICH and ISO guidelines
• Scalable methods applicable to pharmaceuticals, medical devices, food contact materials and consumer electronics
• Streamlined data analysis with integrated libraries, cheminformatics and differential comparison for batch-to-batch consistency

Future Trends and Applications

Emerging directions include increased ion mobility integration for enhanced separation of isomers, machine learning–driven spectral annotation, expanded high-resolution databases and real-time process monitoring. Advances in miniaturized sampling, automation and software interoperability will further accelerate E&L workflows.

Conclusion

Thermo Fisher Scientific’s comprehensive approach to extractables and leachables analysis—combining cutting-edge instrumentation, sophisticated software and curated databases—addresses the complexity of modern safety and quality challenges. This unified platform supports robust identification, structural elucidation and quantitation, ensuring regulatory compliance and protecting consumer health.