Extractable/Leachable Analysis: Using Chromatography, Databases and Mass Spectral Data to Improve Compounds Identification in Commercially Available Catheters

In September 2024, a draft guidance on chemical analysis for biocompatibility assessment of medical devices was published by CDRH at FDA that discussed recommendations and best practices for the collection and reporting of chemical characterization data for submission. The guidance discussed a wide variety of topics, from best practices for sample preparation and extraction, optimization of chromatographic separation methods (GC/MS and LC/MS), utilization of 104 compound E/L standard kit to test system performance and stability, best practices for quantitation and semi-quantitation, and also guidance on compound identification process. The publishing of this guidance and a previously published USP stimuli paper sparked our interest to explore optimizing E/L analysis using both GC/MS and LC/MS and factors that impact optimal compound separation as a factor of analysis time.

Using a newly developed CLAP E/L Standards kit from AChemTek, (104 compounds) and we began to explore how the analytical column (chemistry, diameter, length, pore size); organic mobile phase (MeOH, ACN, IPA), buffers (formic acid, ammonium formate), gradients and flow rate all impacted the separations. Using these experimental RT values, we investigate the use of theoretical RT modeling software, with high-resolution mass spectral data (MS and MSMS), downloadable third-party information managed using ChemVista the database management software to improve the identification of suspect and unknown E&L Compounds.
Three different sets of catheters with different polymer compositions and packaging were analyzed using the Gerstel thermal desorption system integrated with an Agilent 7250 GC/Q-TOF. Solvent extracts (Acidic/Basic Water and 50/50 Ethanol/Water) from the different catheters were also analyzed using GC and LC QTOF's (ESI and APCI). The thermal desorption results provided a quick means to identify potential E/L compounds from that were then confirmed being present in extract samples.