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

Accurate quantitation
during chemical characterizationalso
referred to as extractables and leachables (E&L)within
a toxicological risk assessment for medical device biocompatibility
hinges on the appropriate application of relative response factors
(RRFs). This study investigates the variability of RRFs across a chemically
diverse set of compounds and evaluates the implications of quantitation
model selection on analytical outcomes. Using gas chromatography–mass
spectrometry (GC–MS) and liquid chromatography–mass
spectrometry (LC–MS), we demonstrate that RRFs are highly context-dependent
and influenced by factors such as ionization mode, compound class,
concentration, and instrument conditions. We propose an approach to
RRF determination, emphasizing day-of-analysis calibration and uncertainty
factor modeling to improve reproducibility. Our findings support a
statistically grounded application of analytical evaluation thresholds,
enhancing the reliability of semiquantitative assessments in medical
device biocompatibility.