Redefining GC-MS in the Laboratory with GC Orbitrap

Significance of the Topic

Gas chromatography coupled with high-resolution mass spectrometry (GC-MS) is essential for comprehensive qualitative and quantitative chemical analysis in complex matrices. Recent advances combining GC with Orbitrap mass analyzers deliver unprecedented resolving power and mass accuracy, enabling more confident compound identification, deeper screening capabilities, and robust routine performance in fields such as environmental monitoring, food safety, pharmaceuticals, and metabolomics.

Objectives and Study Overview

This paper introduces the Thermo Scientific™ Q Exactive™ GC Orbitrap™ GC-MS/MS system and its complementary Exactive™ GC variant. The goals are to demonstrate:

• Hybrid quadrupole-Orbitrap architecture integrating GC with high-resolution accurate-mass (HRAM) detection.
• Performance metrics including resolving power, mass accuracy, dynamic range, and acquisition speed.
• Analytical workflows for targeted quantitation, targeted screening, and non-targeted screening.
• Application examples such as pharmaceutical O-ring extractables and pesticide screening.

Methodology

Samples are analyzed by full-scan electron ionization (EI) or chemical ionization (CI) with optional MS/MS in the higher-energy collisional dissociation (HCD) cell. Data acquisition modes include full-scan, timed-SIM, and untargeted screening via deconvolution algorithms in TraceFinder software. Non-targeted screening workflows consist of:

• Accurate-mass deconvolution to extract clean spectra.
• Spectral library searches against high-resolution and unit-mass libraries (e.g., NIST, Wiley).
• High-resolution filtering (HRF) and spectral matching to refine candidate lists.

Instrumentation

The system comprises:

• Thermo Scientific™ Q Exactive™ GC or Exactive™ GC Orbitrap GC-MS platform with resolving power up to 120 000 FWHM at m/z 200.
• TRACE™ 1310 GC system featuring modular injector, ExtractaBrite™ ion source, and vacuum-free column exchange.
• Hybrid optics including C-trap, quadrupole, HCD cell, and Orbitrap mass analyzer.
• ExtractaBrite™ ion source technology with patented RF lens for robust EI/CI performance.
• Typical acquisition parameters: EI at 70 eV, source at 230 °C, transfer line at 280 °C, mass range 50–650 Da, resolution 60 000–120 000 FWHM, lockmass at m/z 207.03235.

Major Findings and Discussion

• Resolving power of 60 000–120 000 enables interference-free detection in complex matrices and confident identification at 5 ppm thresholds.
• Fast full-scan acquisition generates over 15 scans across narrow GC peaks, ensuring accurate peak profiling.
• Mass accuracy consistently better than ±1 ppm across a six-order concentration range without frequent recalibration.
• O-ring extractables study highlighted rapid detection and differentiation of thousands of peaks, with targeted identification using combined spectral matching and HRF scoring.
• Variable electron voltage (VeV) EI enhances molecular ion signals, improving compound confirmation.
• High-resolution metabolomics library provides curated spectra with Kovats indices and elemental compositions for enhanced metabolite profiling.
• MS/MS in the HCD cell yields sub-ppm fragment mass accuracy, supporting structural elucidation via Mass Frontier software.

Benefits and Practical Applications

• Unmatched selectivity for complex sample matrices such as environmental, food, and pharmaceutical extracts.
• Routine high-confidence screening workflows for targeted and non-targeted analysis.
• Extended dynamic range and quantitation capability comparable to triple quadrupole systems in full-scan mode.
• Enhanced structural information through accurate-mass MS/MS fragmentation.
• Robust and user-friendly operation with rapid source changes and column exchanges.

Future Trends and Potential Applications

• Expansion of HRAM spectral libraries for metabolomics, environmental contaminants, and unknown screening.
• Integration of machine learning algorithms for automated deconvolution and identification.
• Development of low-energy ionization techniques (VeV) to improve molecular ion coverage.
• Broader adoption of real-time screening and quantitation in regulatory and industrial laboratories.
• Continuous enhancement of MS/MS fragmentation workflows for structural elucidation of novel compounds.

Conclusion

The Thermo Scientific Q Exactive and Exactive GC Orbitrap GC-MS platforms redefine routine GC-MS analysis by delivering exceptional resolving power, mass accuracy, dynamic range, and flexible acquisition modes. These systems empower analysts with robust workflows for targeted quantitation, comprehensive screening, and confident compound discovery in diverse application areas.

Reference

Makarov A. Hybrid electrostatic trapping for high-resolution mass analysis. Analytical Chemistry. 2000;72(13):1156–1162.