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

Significance of the Topic

Characterizing extractables and leachables in e-cigarette devices is critical to ensure consumer safety, product quality and regulatory compliance. Non-targeted screening helps detect unknown compounds migrating from device materials into e-liquids and aerosols, supporting risk assessment and meeting FDA and EU Tobacco Product Directive requirements.

Objectives and Study Overview

This study aimed to develop a unified non-targeted analytical workflow using a single UPLC-APGC-QTOF-MS platform to profile extractable and leachable compounds from various components of disposable and refillable e-cigarette devices. Key objectives included comprehensive chemical screening and automatic compound identification.

Methodology

• Separate extraction of individual device parts: inner and outer end caps, packaging cap, paper wrap, metal shell, gauze and flavor formulation.
• Use of isopropanol blanks for background subtraction and differential screening.
• Combined liquid chromatography (UPLC) and gas chromatography (GC) analyses on a single high-resolution QTOF-MS.
• Data acquisition in alternating low/high collision energy mode (MSE) across full mass range to capture precursor and fragment ion spectra.
• Automated data processing against an extractables and leachables library using UNIFI software, applying accurate mass, retention time, isotopic fit and fragmentation matching.

Instrumentation Used

• UPLC: ACQUITY UPLC I-Class system
• GC: ACQUITY UPC² coupled with APGC ion source
• Mass spectrometer: Xevo G2-XS QTof operating with MSE acquisition
• Data analysis: UNIFI scientific information system

Main Results and Discussion

The workflow enabled detection and tentative identification of over a dozen compounds across device components, including:

• Dibutyl phthalate and dioctyl sebacate (plasticizers)
• Octadecanoic acid (surfactant/softening agent)
• Sorbic acid (preservative)
• 4-Methyl benzophenone (stabilizer)
• N,N-Dimethyl-p-phenylenediamine and HMBTAD (light stabilizers)
• Disperse Red 11 (dye)
• Uvinul 120 and Irgafos 168 (anti-oxidants)

Automated library matching significantly streamlined data review, while sample comparison tools highlighted component-specific extractables.

Benefits and Practical Applications

• Single-platform analysis reduces method development time and instrument overhead.
• High-resolution accurate mass data with MSE enhances confidence in identifications.
• Integrated informatics accelerates screening and reporting for quality control and regulatory submissions.
• Technique adaptable to other inhalation or packaged consumer products for extractables and leachables studies.

Future Trends and Potential Uses

Emerging directions include expanding spectral libraries with more packaging and device materials, integrating AI-based compound identification, applying the workflow to aerosol emissions, and automating sample handling and data interpretation for high-throughput screening.

Conclusion

This study demonstrates that a unified UPLC-APGC-QTOF-MS platform with MSE acquisition and advanced informatics delivers a robust, non-targeted approach to characterize extractables and leachables from e-cigarette components, enhancing safety assessment and regulatory compliance.

References

• Naren Meruva; Baiba Cabovska; Rainer Rozenich; Dimple Shah; Kari Organtini; Gareth Cleland. Non-Targeted Screening of Extractables and Leachables in E-Cigarettes Using a Single Platform UPLC-APGC-QTOF-MS. Waters Corporation, Milford, MA, 2017.