Screening Workflow Using Ion Mobility-Mass Spectrometry for The Analysis of Extractables and Leachables

Importance of the Topic

Extractable and leachable (E&L) analysis is essential in regulated industries such as pharmaceuticals, cosmetics, and food packaging. Unwanted compounds migrating from packaging or contact materials can pose safety risks and must be identified and quantified to meet global regulatory standards.

Objectives and Study Overview

This application note presents a streamlined workflow combining targeted and non-targeted screening of E&L components using ion mobility–high-resolution mass spectrometry (IMS-HRMS) within the UNIFI Scientific Information System. Key goals include building a comprehensive scientific library, implementing rapid screening, and enabling structural elucidation of unknowns.

Methodology and Instrumentation

Samples of packaging materials were prepared by cutting into small pieces and sonicating in 2-propanol. Chromatographic separation was performed on an ACQUITY UPLC I-Class FTN system with a CORTECS C18 column under a water/methanol gradient. Mass analysis used a Vion IMS QTof instrument operating in HDMSE mode over m/z 50–1500 in both ESI+ and ESI–. Software control, data processing, and library management were handled by UNIFI Scientific Information System v1.9.4. System suitability standards bracketing the sample injections ensured mass accuracy (≤3 ppm) and CCS reproducibility (≤2%).

Instrumentation

• ACQUITY UPLC I-Class FTN with binary solvent delivery
• CORTECS C18 column (2.1×100 mm, 1.6 µm) maintained at 40 °C
• Vion IMS QTof with ESI source and HDMSE acquisition
• UNIFI Scientific Information System v1.9.4 for acquisition, library creation, screening, and reporting

Key Results and Discussion

A bespoke scientific library of over 100 E&L compounds was created, incorporating experimentally derived retention times, CCS values, adducts, and fragment ions. Targeted screening against this library reduced false positives by leveraging multiple identification points (accurate mass, retention time, CCS, fragments). Ion mobility separation improved spectral clarity by aligning precursor and fragment drift times, facilitating cleaner low- and high-energy spectra. Non-targeted screening employed binary comparison to highlight sample-specific peaks against blanks, followed by UNIFI’s elucidation toolkit. This tool calculated elemental compositions, searched chemical databases, and performed in-silico fragmentation to propose candidate structures.

Benefits and Practical Applications

The described workflow offers:

• Integrated targeted and non-targeted screening in a single application
• Enhanced confidence through CCS as an orthogonal separation dimension
• Faster unknown identification via automated elucidation tools
• Customizable reporting and multi-stage data review

Future Trends and Opportunities

Emerging developments may include:

• Expanded E&L libraries enriched with CCS reference values
• Advanced machine-learning algorithms for feature prioritization
• Integration of multivariate statistics and artificial-intelligence-driven elucidation
• Quantitative IMS-HRMS workflows for absolute migration assessments

Conclusion

The UNIFI-enabled IMS-HRMS workflow integrates targeted and non-targeted E&L screening, combining high-resolution mass analysis, ion mobility separation, and automated data processing. This approach accelerates library creation, improves identification confidence, and streamlines unknown compound elucidation, delivering robust results for regulatory compliance and product safety.

References

1. Food and Drug Administration, 2000, Code of Federal Regulation Chapter 21.
2. Official Journal of the European Union, 2004, Regulation 1935/2004/EC.
3. Official Journal of the European Union, 2006, Regulation 2023/2006/EC.
4. Official Journal of the European Union, 2011, Regulation 10/2011/EU.
5. Official Journal of the European Union, 2006, Regulation 1907/2006/EC.
6. Official Journal of the European Union, 2009, Regulation 2009/49/EC.
7. Official Journal of the European Union, 1987, Directive 87/357/EEC.
8. The Use of Collision Cross Section (CCS) Measurements in Food and Environmental Analysis, Technical Note 720005374EN, 2015.
9. Using Ion Mobility for Enhanced Spectral Cleanup in Food and Environmental Analysis, Technical Note 720005375EN, 2015.
10. Extractables & Leachables Screening Standard. Care and Use Manual 720005660EN, 2016.
11. Screening Workflow for Extractable Testing Using the UNIFI Scientific Information System, Technical Note 720005688EN, 2016.
12. Quantitation of High Resolution MS Data Using UNIFI: Application Note 720005605EN, 2016.