Routine High Resolution Mass Spectrometry (HRMS) for the Screening of Extractables and Leachables (E&Ls) Using the Waters™ ACQUITY™ RDa™ Mass Detector

Significance of the Topic

The reliable detection and identification of extractables and leachables (E&Ls) is essential for ensuring the safety and compliance of pharmaceutical products, medical devices, food contact materials, and consumer goods. High resolution mass spectrometry (HRMS) offers the selectivity and accuracy needed to characterize trace-level contaminants. However, traditional HRMS platforms often demand specialized expertise and complex workflows, limiting their routine application in regulated laboratories.

Objectives and Study Overview

This study demonstrates a streamlined HRMS workflow for routine E&L screening using the Waters ACQUITY RDa Mass Detector coupled with UNIFI Software. A standard mixture of eighteen common polymer additives was analyzed to evaluate mass accuracy, compound identification confidence, and ease of use. The goal was to establish a robust platform accessible to both expert and non-expert users.

Methodology

Samples of the E&L screening standard were injected directly without sample preparation. Full-scan accurate mass data were acquired in positive ion mode, incorporating a scheduled lockmass correction to maintain mass stability over extended runs. High and low energy spectra were collected simultaneously via cone voltage ramping, enabling automatic assignment of fragment ions and enhancing compound confirmation.

Instrumentation

• Waters ACQUITY RDa Mass Detector with auto-tune and mass calibration functions
• Waters UNIFI Software within the waters_connect informatics platform
• ACQUITY BEH C18 column operated at 70 °C to improve chromatographic separation without column degradation

Main Results and Discussion

All eighteen polymer additives were detected and identified with mass accuracy ≤ 3.1 ppm. The automated UNIFI screening workflow matched accurate mass and fragmentation patterns against built-in libraries, eliminating manual data interpretation. The scheduled lockmass feature provided stable mass measurement over time while reducing reagent consumption.

Benefits and Practical Applications

• Consistent sub-5 ppm mass accuracy for routine E&L compounds
• Automatic acquisition of fragmentation data to increase identification confidence
• Intuitive software interface enables non-expert users to perform HRMS analysis
• Compliant-ready UNIFI platform supports regulated workflows
• High-temperature BEH column technology ensures robust separation without degradation

Future Trends and Potential Applications

Advances in HRMS instrumentation and informatics will further democratize E&L screening, enabling real-time monitoring and broader adoption in pharmaceutical, medical device, and food safety laboratories. Integration with cloud-based data sharing, machine learning for compound prediction, and expanded library databases will enhance throughput and analytical confidence.

Conclusion

The Waters ACQUITY RDa Mass Detector combined with UNIFI Software provides a powerful yet user-friendly platform for routine HRMS screening of extractables and leachables. This workflow delivers high mass accuracy, automated compound identification, and flexible operation suited to both expert and non-expert analysts.

References

1. ICH Q3E: Guideline for Extractables and Leachables.
2. FDA Guidance for Industry: Container Closure Systems for Packaging Human Drugs and Biologics.
3. EMA Guideline on Plastic Immediate Packaging Materials.
4. FDA Deeming Regulation on Electronic Nicotine Delivery Systems, 2016.
5. Wyndham K.D., Walter T.H., Iraneta P.C., et al. A Review of Waters Hybrid Particle Technology, Part 2: BEH Technology. Waters White Paper, 2004.