Targeted and Untargeted Screening of ‘e- liquids’ Using the High Resolution ACQUITY™ RDa™ Mass Detector

Importance of the Topic

The rapid growth of electronic nicotine delivery systems (ENDS) has raised concerns about the chemical composition and safety of ‘e-liquids.’ Routine screening for both known and unknown constituents is essential to ensure product quality, detect potentially harmful species such as carbonyl-containing compounds, and support regulatory and research demands in analytical and industrial laboratories.

Objectives and Study Overview

This application note demonstrates a combined targeted and untargeted screening workflow for a nicotine-free, strawberry-flavored e-liquid using the high-resolution ACQUITY RDa Mass Detector coupled to UPLC. A commercially available extractables and leachables (E&L) library within UNIFI software was employed to identify major components, while unknown peaks were annotated using the UNIFI Elucidation Toolset and online chemical databases.

Methodology and Instrumentation

• Sample Preparation: Dilution of 0.5% w/v in 98:2 mobile phase (A:B).
• UPLC System: ACQUITY UPLC I-Class Premier, Premier BEH C18 column (100×2.1 mm, 1.7 µm), 70 °C column, 10 °C sample temperature, 5 µL injection, 0.4 mL/min flow.
• Mobile Phases: A = 2 mM ammonium formate/0.1% formic acid; B = methanol/0.1% formic acid; gradient 2→99% B over 8.5 min.
• Mass Detection: ACQUITY RDa, full-scan MS with fragmentation (60–150 V ramp) in positive (1.0 kV capillary) and negative (0.8 kV) electrospray, 50–2000 m/z range, 500 °C desolvation.
• Data Processing: UNIFI 3.6 with waters_connect 4.1; E&L library screening and Elucidation Toolset for unknowns.

Key Results and Discussion

System suitability with E&L standard showed mass errors <±3.4 ppm (positive) and <±3.7 ppm (negative). Optimized column temperature (70 °C) and a 95:5 MeOH:acetone needle wash minimized carryover of antioxidant Irganox 245. In positive mode, 33 components were confidently identified (19 containing carbonyl groups), including cinnamaldehyde. Negative mode yielded five more compounds. A prominent unknown at 227.1643 m/z was elucidated as Hedione (C₁₃H₂₂O₃) by isotopic fitting and online library matching.

Benefits and Practical Applications

• Routine sub-5 ppm mass accuracy screening without specialist HRMS expertise.
• Simultaneous high/low energy acquisition for confident fragment-based ID.
• Automated UNIFI workflows for acquisition, processing, and reporting.
• In-built and online libraries enable rapid targeted and untargeted analysis.

Future Trends and Potential Applications

Integration of AI-driven spectral interpretation and expanded spectral libraries will accelerate unknown identification. Coupling RDa screening with quantitative methods for carbonyl compounds could support regulatory monitoring. Portable high-resolution MS platforms may enable on-site quality control for e-liquid manufacturing.

Conclusion

The ACQUITY RDa system combined with UNIFI software offers a robust, user-friendly solution for comprehensive targeted and untargeted screening of e-liquids. High mass accuracy, fragmentation data, and elucidation tools ensure reliable identification of known additives and unknown contaminants, addressing safety and quality concerns in ENDS products.

References

1. McDermott MS et al. Addiction. 2021;116(10):2825–2836.
2. Mishra A et al. Indian J Pediatr Oncol. 2015;36(1):24–31.
3. Gholap VV et al. J Anal Methods Chem. 2018;2018:1720375.
4. Schober W et al. Int J Hyg Environ Health. 2013;217:628–637.
5. Famele M et al. Nicotine Tob Res. 2015;17(3):271–279.
6. Bekki K et al. Int J Environ Res Public Health. 2014;11(11):11192–11200.
7. Menicagli R et al. Int J Prev Med. 2020;11:53.
8. Waters Corp. Review of BEH Technology.
9. Nistoriak MA et al. Toxicol In Vitro. 2019;61:104648.
10. PubChem. https://pubchem.ncbi.nlm.nih.gov.
11. ChemSpider. https://www.chemspider.com.