Comprehensive chemical characterization of e-cigarette liquids using high-resolution Orbitrap GC-MS

Importance of the topic

Electronic cigarette liquids contain a complex mixture of solvents, flavorings, nicotine and other additives with potential health implications. Comprehensive chemical profiling of these e-liquids is essential for regulatory compliance, quality control, and assessment of toxicological risk.

Study objectives and overview

The study aimed to demonstrate the capability of high-resolution, accurate-mass Orbitrap GC-MS coupled with solid phase micro-extraction (SPME) Arrow for both targeted screening of known harmful and potentially harmful constituents (HPHCs) and non-targeted profiling of additional e-liquid components.

Methodology and instrumentation

Ten commercially available e-liquid samples (flavored and unflavored, nicotine levels of 0, 6 or 12 mg/mL) were analyzed. Samples were diluted in water, spiked with 8-hydroxyquinoline internal standard, and introduced via SPME Arrow using a TriPlus RSH autosampler. Chromatographic separation employed a TRACE 1310 GC with TG-WaxMS column. The Exactive GC Orbitrap mass spectrometer was operated under electron ionization (EI) and chemical ionization (positive and negative CI) at 60 000 FWHM resolution, acquiring full-scan data across 35–400 Da. Data processing and deconvolution were performed with Thermo Scientific TraceFinder software.

Main results and discussion

Targeted screening against a custom HPHC database enabled confident detection of key compounds such as nicotine, piperonal, cinnamic acid methyl ester and various flavor volatiles with mass errors below 2 ppm. Non-targeted deconvolution and spectral library matching identified over twenty additional constituents, including vanillin, menthol, eugenol, and γ-decalactone. Soft ionization (PCI and NCI) confirmed molecular ions and characteristic adducts ([M+H]+, [M+C2H5]+, [M+C3H5]+) for select analytes, enhancing specificity.

Benefits and practical applications

The combined Orbitrap GC-MS and SPME Arrow approach offers

• High mass accuracy and resolution for unambiguous identification
• Automated deconvolution workflows for rapid non-targeted screening
• Solvent-free sample enrichment and improved sensitivity
• Capability to detect both regulated HPHCs and unexpected contaminants

This workflow supports regulatory monitoring, product development, and quality assurance in analytical and industrial laboratories.

Used instrumentation

• Thermo Scientific Exactive GC Orbitrap mass spectrometer
• Thermo Scientific TRACE 1310 Gas Chromatograph
• Thermo Scientific TriPlus RSH SPME Arrow autosampler
• TRACEGOLD TG-WaxMS capillary column (30 m × 0.25 mm × 0.25 μm)
• TraceFinder data processing and deconvolution software

Future trends and possibilities

Advances may include integration of real-time data analytics, expansion of accurate-mass spectral libraries, automated quantitation modules, and application to novel vaping formulations. Coupling with orthogonal detectors and enhanced CI reagent gases could further improve coverage of emerging contaminants.

Conclusion

The high resolution accurate mass GC-MS technique combined with SPME Arrow sampling provides a powerful, streamlined solution for comprehensive qualitative profiling of e-liquids. Its sensitivity, selectivity, and automated workflows address both targeted regulatory needs and exploratory non-targeted analyses.

References

1. Barrington-Trimis JL, Samet JM, McConnell R. JAMA 2014;12:2493–2494.
2. U.S. FDA. Harmful and Potentially Harmful Constituents in Tobacco Products and Tobacco Smoke.
3. U.S. FDA Draft Guidance: Reporting HPHCs under FD&C Act Section 904(a)(3).
4. U.S. FDA Draft Guidance: PMTA for ENDS under FD&C Act Section 910.
5. EU Tobacco Products Directive 2014/14/EU.
6. WHO Framework Convention on Tobacco Control, 2003.
7. UK MHRA e-cigarette regulations.
8. Kremser A, Jochmann MA, Schmidt T. Anal Bioanal Chem. 2016;408:943–952.