Challenging the Database: Day-of-Analysis Calibration and UF Modeling for Reliable RRF Use in Medical Device Chemical...

Area of Science:

• Analytical Chemistry
• Materials Science
• Toxicology

Background:

• Accurate quantitation of extractables and leachables (E&L) is crucial for medical device biocompatibility.
• Relative response factors (RRFs) are essential for toxicological risk assessment but exhibit variability.
• Current methods for RRF determination may not fully account for analytical complexities.

Purpose of the Study:

• To investigate the variability of RRFs across diverse chemical compounds.
• To evaluate the impact of different quantitation models on analytical outcomes.
• To propose an improved approach for RRF determination to enhance reproducibility.

Main Methods:

• Utilized gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS).
• Analyzed a chemically diverse set of compounds to assess RRF variability.
• Evaluated the influence of ionization mode, compound class, concentration, and instrument conditions on RRFs.

Main Results:

• Demonstrated that RRFs are highly context-dependent.
• Identified significant influence of ionization mode, compound class, concentration, and instrument conditions on RRFs.
• Showcased the variability of RRFs across different analytical scenarios.

Conclusions:

• Emphasized the need for statistically grounded application of analytical evaluation thresholds.
• Proposed an approach for RRF determination using day-of-analysis calibration and uncertainty factor modeling.
• Enhanced the reliability of semiquantitative assessments in medical device biocompatibility evaluations.