Screening Workflow for Extractables Testing of Medical Devices Using the UNIFI Scientific Information System

Importance of the Topic

The characterization of extractables from medical devices and their packaging is critical to ensuring patient safety and regulatory compliance. With global standards such as ISO 10993-18 mandating thorough evaluation of leachable and extractable compounds, analytical laboratories require robust, efficient workflows to detect, identify, and quantify known and unknown components. Automating data processing and structural elucidation accelerates decision-making and reduces the burden on skilled analysts.

Study Objectives and Overview

This application brief describes a streamlined screening workflow implemented in the UNIFI Scientific Information System for extractable analysis of medical devices. The goals are to demonstrate how an integrated informatics platform can:

• Support targeted screening against a custom scientific library
• Enable non-targeted discovery of unknown compounds using high-resolution MS
• Facilitate statistical comparison between sample groups
• Automate structural elucidation and reporting

Methodology and Instrumentation

The workflow combines non-targeted MSE or HDMSE data acquisition on quadrupole time-of-flight (QTof) or ion mobility QTof (IMS-QTof) instruments with liquid, gas, or convergent chromatography separations:

• Chromatography options: UPLC, APGC (gas chromatography), or UPC (convergence chromatography)
• Mass spectrometry: QTof operated in alternate low/high collision energy MSE mode for simultaneous precursor and fragment ion collection; IMS-QTof adds collisional cross section (CCS) measurements.
• Software platform: UNIFI Scientific Information System for data processing, library screening, multivariate analysis (PCA, PLS-DA, OPLS-DA via EZInfo), and structural discovery.

Main Results and Discussion

The UNIFI workflow proceeds in several stages:

• Library creation: Analysts build a scientific library containing compound names, formulas, structures, CCS values, reference spectra, and metadata to support targeted screening.
• Targeted screening: Raw data are processed against the library with user-defined mass accuracy and retention time tolerances, fragment match requirements, and CCS deltas to flag known extractables.
• Statistical comparison: Binary Compare identifies components unique to sample versus blank. Multivariate tools (PCA, PLS-DA, OPLS-DA) highlight markers distinguishing groups of samples.
• Discovery and elucidation: The Discovery tool ranks candidate elemental compositions by accurate mass, isotope pattern, fragment matching, and database hits (ChemSpider) to propose structures. Analysts assign identities and update the library for future runs.
• Reporting: A customizable report template embedded in the analysis method compiles chromatograms, spectra, statistical plots, and target summary tables.

Benefits and Practical Applications

This integrated approach delivers multiple advantages for extractable screening:

• Reduces analyst time and expertise required for structural elucidation by automating fragment match and database search.
• Supports both targeted and non-targeted screening in a single run, minimizing sample consumption and instrument time.
• Enables rapid comparison of multiple sample sets to detect process-related impurities or degradants.
• Ensures compliance with ISO 10993-18 through clear documentation and validation of acceptance criteria.

Future Trends and Opportunities

As regulatory expectations evolve and material complexity increases, future developments may include:

• Expanded CCS libraries for enhanced confidence in ion mobility-based identifications.
• Machine learning algorithms to predict fragmentation patterns and flag novel structures.
• Cloud-based collaboration for sharing scientific libraries and methodologies across global sites.
• Integration with real-time monitoring systems for in-line extractable screening during manufacturing.

Conclusion

The UNIFI Scientific Information System provides a unified, automated workflow for comprehensive extractable screening of medical devices and packaging. By leveraging high-resolution MS, custom libraries, statistical tools, and database-driven discovery, analysts can identify both known and unknown components more efficiently, ensuring product safety and regulatory compliance.

Reference

1. McCullagh M., Hanot V., Goscinny S. Use of Ion Mobility Spectral Cleanup and Collision Cross Section Values to Increase Confidence and Efficiency in Pesticide Residues Screening Strategies. Waters Application Note, June 2014.
2. Cabovska B. Non-Targeted Screening Analysis of Packaging Extracts Using the UNIFI Scientific Information System. Waters Application Note, March 2015.