Qualitative and Quantitative Analysis of Electronic Cigarette Liquids using Gas Chromatography Orbitrap Mass Spectrometry

Significance of the Topic

Electronic cigarettes have rapidly gained global popularity as an alternative to traditional tobacco products. Despite widespread use, the chemical composition of e-liquids—including flavorings, solvents, and potential toxicants—remains incompletely understood. Regulatory bodies such as the FDA and EU TPD mandate monitoring of harmful constituents, creating a critical need for analytical methods that deliver high confidence in both known and unknown compound identification.

Objectives and Study Overview

This work demonstrates the efficacy of combining solid-phase microextraction (SPME Arrow) with high-resolution GC-Orbitrap mass spectrometry for comprehensive qualitative and quantitative analysis of electronic cigarette liquids. The study covers targeted screening of FDA-listed harmful and potentially harmful constituents (HPHCs), untargeted compound discovery, and precise measurement of nicotine concentrations across a broad dynamic range.

Methodology and Instrumentation

The experimental approach involved:

• Optimization of SPME Arrow conditions: fiber selection, incubation, extraction temperature, and duration.
• Gas chromatographic separation using a Thermo Scientific TRACE 1310 GC fitted with a TG-WAXMS capillary column and TriPlus RSH autosampler.
• Mass spectrometric detection on an Exactive GC Orbitrap MS operated in electron ionization (EI) full-scan mode and positive/negative chemical ionization (PCI, NCI) for confirmatory analyses.
• Data processing with Thermo Scientific TraceFinder software, featuring automated spectral deconvolution and library matching with sub-ppm mass accuracy.

Instrumentation Used

• Thermo Scientific Exactive GC Orbitrap Mass Spectrometer
• Thermo Scientific TRACE 1310 Gas Chromatograph
• Thermo Scientific TriPlus RSH Autosampler
• SPME Arrow Extraction System
• TG-WAXMS Capillary Column

Main Results and Discussion

Targeted screening against an in-house compound database enabled confident detection of FDA-listed HPHCs in flavored and unflavored e-liquids. Untargeted analysis with spectral deconvolution revealed additional constituents such as p-cymene, confirmed by matching EI spectra and chemical ionization adduct patterns. Quantitative determination of nicotine via split/splitless injection demonstrated linearity (R2=0.9991) over 46–13 792 ng/mL, mass accuracy below 1 ppm, and precision with RSD < 3%.

Benefits and Practical Applications

• High resolving power and automated deconvolution streamline both targeted and non-targeted workflows.
• Chemical ionization modes enhance specificity for compound confirmation.
• SPME Arrow provides solvent-free, automated sample preparation compatible with routine autosampler operations.
• Method supports regulatory compliance by enabling comprehensive monitoring of harmful constituents.

Future Trends and Opportunities

Expanding spectral libraries and integrating machine learning for automated compound identification will further enhance untargeted screening capabilities. The development of compact GC-MS systems and online monitoring approaches could enable real-time quality control. Standardized protocols aligned with evolving regulatory requirements will support robust safety assessments of emerging e-liquid formulations.

Conclusion

The combination of SPME Arrow sample introduction with Exactive GC Orbitrap GC-MS offers a powerful, high-confidence platform for both qualitative and quantitative analysis of electronic cigarette liquids, meeting stringent demands for mass accuracy, sensitivity, and selectivity.

Reference

1. Barrington-Trimis JL, Samet JM, McConnell R. Flavorings in electronic cigarettes: an unrecognized respiratory health hazard. JAMA 2014;12:2493–2494.
2. U.S. Food and Drug Administration. Harmful and Potentially Harmful Constituents in Tobacco Products and Tobacco Smoke. Established List under the FDA.
3. FDA Guidance for Industry: Reporting Harmful and Potentially Harmful Constituents in Tobacco Products and Tobacco Smoke Under Section 904(a)(3) of the FD&C Act. Draft Guidance.
4. FDA Guidance for Industry: Premarket Tobacco Product Applications for Electronic Nicotine Delivery Systems under Section 910 of the FD&C Act. Draft Guidance.
5. European Commission. The Tobacco Products Directive (2014/14/EU).
6. World Health Organization. Framework Convention on Tobacco Control. 2003.
7. Medicines and Healthcare products Regulatory Agency. E-cigarettes: regulations for consumer products.
8. Kremser A, Jochmann MA, Schmidt TC. Systematic comparison of static and dynamic headspace sampling techniques for gas chromatography. Anal Bioanal Chem 2016;408:943–952.