NON-TARGETED SCREENING OF EXTRACTABLES AND LEACHABLES IN E-CIGARETTES USING A SINGLE PLATFORM UPLC-APGC-QTOF-MS

Importance of the Topic

E-cigarette devices and their components can release a variety of chemical compounds into inhalation aerosols. Comprehensive non-targeted screening of extractables and leachables ensures consumer safety, regulatory compliance and product quality in the fast-growing inhalation tobacco market.

Objectives and Study Overview

This study aimed to develop a unified analytical workflow combining ultraperformance liquid chromatography (UPLC) and atmospheric pressure gas chromatography (APGC) coupled to quadrupole time-of-flight mass spectrometry (QTOF-MS) for non-targeted profiling of extractables and leachables from e-cigarette components. Individual cartridge parts were extracted and screened to identify known and unknown migrating compounds.

Methodology and Instrumentation

Sample Preparation:

• Separate isopropanol extractions of inner end cap, outer end cap, packaging cap, paper wrap, metal shell, gauze and e-liquid formulation.

Chromatographic Conditions:

• LC separation on ACQUITY UPLC I-Class with reversed-phase column in positive electrospray ionization (ESI+) mode.
• GC separation on APGC-GC G2-XS QTOF in atmospheric pressure GC mode.

Mass Spectrometry and Data Processing:

• MSE data acquisition alternating low and high collision energies across full mass range.
• Compound identification using UNIFI software with accurate mass, isotopic fit, fragment matching and retention time criteria.

Main Results and Discussion

The combined UPLC-APGC-QTOF-MS platform enabled detection of diverse classes of extractables and leachables. Key findings included:

• Plasticizers such as dibutyl phthalate and dioctyl sebacate identified in end caps.
• Surfactants and softening agents like octadecanoic acid in packaging materials.
• Stabilizers and antioxidants including 4-methyl benzophenone, Uvinul 120 and Irgafos 168 across several components.
• Specialty additives such as HMBTAD light stabilizer and Disperse Red 11 dye in polymer parts.

Comparative analysis against reagent blanks highlighted unique markers per device component. The use of accurate mass full-scan data with fragment spectra facilitated confident annotation of unknowns.

Benefits and Practical Applications

The integrated UPLC-APGC-QTOF-MS approach offers:

• Comprehensive coverage of semi-volatile to non-volatile migrants in one platform.
• Rapid non-targeted screening to support material selection and supplier qualification.
• Enhanced data confidence via library matching and automated reporting in UNIFI.

This workflow supports regulatory submissions under FDA Deeming Regulations and EU Tobacco Product Directive by demonstrating product safety through exhaustive chemical profiling.

Future Trends and Potential Applications

Advancements may include:

• Expansion of custom spectral libraries for broader compound coverage.
• Integration of ion mobility separation to improve isomer resolution.
• Automation of sample preparation and data interpretation for high throughput screening.
• Application of this platform to next-generation inhalation devices and novel e-liquid formulations.

Conclusion

The study demonstrates that a single UPLC-APGC-QTOF-MS platform with MSE acquisition and advanced informatics can effectively characterize a wide range of extractables and leachables in e-cigarette components. This unified workflow enhances analytical efficiency, data reliability and supports regulatory compliance for inhalable consumer products.

References

Naren Meruva et al. Non-targeted screening of extractables and leachables in e-cigarettes using a single platform UPLC-APGC-QTOF-MS, Waters Corporation, 2017