Analysis of Extractables and Leachablesin Catheters Using Accurate Mass Libraries and High-Resolution GC/MS and LC/MS

Significance of the topic

Medical device components may release extractables and leachables (E&L) into patient contact media, posing safety and regulatory concerns. Accurate identification of these compounds is essential for risk assessment and quality control in pharmaceutical and medical device industries.

Objectives and Study Overview

This study evaluates a combined workflow using high-resolution gas and liquid chromatography–mass spectrometry (GC/Q-TOF and LC/Q-TOF) to comprehensively characterize E&L in catheter materials from three suppliers. Key goals include developing accurate mass libraries for suspect screening and comparing targeted and non-targeted approaches to profile extractables over multiple extraction time points.

Methodology and Instrumentation

Catheters composed of PVC or silicone-coated natural rubber latex were extracted with 1:1 ethanol/water at 37 °C for 24 h, 48 h, and 7 days. Analyses were performed with:

• GC/Q-TOF: Agilent 8890 GC coupled to 7250 Q-TOF, DB-5Q column, splitless injection, 50–1000 m/z range.
• LC/Q-TOF: Agilent 1290 Infinity II with Revident LC/Q-TOF, PS AQ-C18 column, water/methanol gradient with ammonium formate and formic acid, positive ESI, MS/MS acquisition.

Main Results and Discussion

• Over 400 EI spectra were compiled into a custom accurate mass E&L library, annotated for fragment formulas.
• Suspect screening identified common plasticizers, antioxidants, bisphenols, and nitrosamines in catheter extracts, with variations between materials and extraction times.
• Non-targeted analysis revealed clusters distinct to each catheter type, confirmed by principal component analysis.
• LC/Q-TOF complemented GC/Q-TOF by detecting more polar or higher-mass E&L species, including sulfur-containing compounds in latex-based catheters.

Benefits and Practical Applications

This integrated GC-MS and LC-MS strategy offers:

• Enhanced coverage of diverse E&L chemistries.
• Accelerated compound identification through accurate mass libraries.
• Robust workflows for regulatory compliance and product safety assessment.

Future Trends and Potential Applications

• Expansion of accurate mass libraries to include emerging monomers and degradants.
• Automation of suspect and non-targeted workflows with AI-driven data mining.
• Adaptation to other medical devices and packaging materials for comprehensive E&L surveillance.

Conclusion

The combined high-resolution GC/Q-TOF and LC/Q-TOF workflow, supported by custom accurate mass libraries, enables comprehensive and reliable profiling of extractables and leachables in catheter materials, facilitating improved safety evaluations.