Improved identification of extractable and leachable substances with Orbitrap Exploris GC 240

Význam tématu

Assessing extractable and leachable (E&L) substances from polymeric materials is critical for ensuring safety and compliance in pharmaceutical, medical device, and food packaging applications. High-resolution accurate-mass (HRAM) GC-MS workflows offer improved sensitivity and selectivity, enabling comprehensive profiling of potential contaminants released under worst-case extraction conditions.

Study objectives and overview

This study evaluates the performance of the Thermo Scientific Orbitrap Exploris GC 240 mass spectrometer combined with Thermo Scientific Compound Discoverer software. Key goals include demonstrating enhanced detection, spectral deconvolution, and confident identification of known and unknown E&L compounds from rubber stopper extracts.

Materials and methods

• Sample preparation followed ISO 10993-12, extracting pharmaceutical rubber stoppers with isopropanol (IPA) and dichloromethane (DCM) at 50 °C for 72 h.
• Automated liquid injection employed a Thermo Scientific TriPlus RSH SMART autosampler.
• GC-MS data were acquired in full scan mode using electron impact (EI) and positive chemical ionization (PCI) on the Orbitrap Exploris GC 240.
• Chromatography Data System: Chromeleon CDS 7.3.2; unknown analysis: Compound Discoverer 3.3 SP2.

Used instrumentation

• Orbitrap Exploris GC 240 mass spectrometer: up to 240 000 FWHM at m/z 200 and <1 ppm mass accuracy.
• TriPlus RSH SMART autosampler for reproducible injections.
• Chromeleon CDS 7.3.2 for sequence control and data acquisition.
• Compound Discoverer 3.3 SP2 for deconvolution, background subtraction, and library matching.

Results and discussion

• A total of 929 compounds were detected; 695 unknown E&L substances remained after blank subtraction and spectral deconvolution.
• Comparison of GC-HRAM versus LC-HRAM for 2,4-di-tert-butylphenol showed 127× greater molecular ion response in GC mode.
• High mass resolving power and sub-ppm accuracy enabled unambiguous elemental composition proposals and library matches with mass errors <0.01 ppm.
• Case example: 3,5-di-tert-butyl-4-hydroxybenzaldehyde was confirmed by extracted ion chromatograms, molecular ion [M–e]+ (234.16144 m/z), PCI [M+H]+ and [M+C2H5]+ adducts, and spectral matching.
• An initially misidentified compound (hexadecanoic acid) was corrected by retention time comparison and molecular ion evidence in PCI mode.

Benefits and practical applications

The Orbitrap Exploris GC 240 with Compound Discoverer streamlines non-targeted E&L workflows by improving sensitivity for low-abundance analytes, simplifying unknown identification, and providing high confidence in structural assignments. This approach supports regulatory submissions, quality control, and risk assessments in pharmaceutical and medical device industries.

Future trends and opportunities

Advances may include expanded high-quality HRAM spectral libraries for E&L substances, integration of machine learning for automated feature prioritization, and extension of workflows to other packaging materials and biologically relevant matrices. Coupling HRAM GC-MS with orthogonal techniques and real-time data analysis promises further gains in throughput and identification confidence.

Conclusion

Incorporating the Orbitrap Exploris GC 240 and Compound Discoverer software significantly enhances detection, deconvolution, and identification of E&L compounds. High mass resolution, accuracy, and dual ionization modes deliver robust workflows for comprehensive profiling of extractable and leachable substances.

Reference

• Roberts D., Warner N., Zheng X., Cole J., Lu D., Liu C., Zhang N., Hackbusch S., Kutscher D. Improved identification of extractable and leachable substances with Orbitrap Exploris GC 240. Thermo Fisher Scientific, 2024.
• ISO 10993-12 Biological evaluation of medical devices – Sample preparation and reference materials, 2012.