Polyethersulfone in-line filters: an extractible study in the context of chemotherapy administration

Introduction
In-line filters are widely used during chemotherapy administration, in particular to remove particles during the infusion. They are most commonly composed of a polyethersulfone (PES) filter membrane and a modified acrylic housing. Recent studies reporting cases of allergic hypersensitivity reactions during etoposide infusions using in-line filters suggest a potential container-content interaction involving filter compounds. This study aimed to identify and characterize extractable compounds from PES filters that may contribute to these adverse reactions, thereby enhancing chemotherapy safety protocols.

Materials and Methods
We analysed three in-line 0.22 µm filters (F1, F2 and F3) supplied from three different manufacturers. Each device was disassembled into its constituent PES membrane and housing components. The extractions were then performed for 24 hours at 37°C, following ISO-10993-12 guidelines, in four extraction solvents of various polarity in order to extract a wide range of compounds: isopropanol (IPA), hexane (non-polar), aqueous buffer at pH 3 and pH 9 (simulating extreme pH of injectable drug solutions). Extracts were analysed by gas chromatography-mass spectrometry, with aqueous extracts undergoing a prior liquid-liquid extraction using dichloromethane. Identification was performed by comparison with the National Institute of Standards and Technology (NIST2020) mass spectra library. Each experiment was performed in triplicate and blank samples were processed in the same way as real samples to check for contamination. A literature review was carried out to identify potentially allergenic compounds out of those recognized.

Results
We detected 43, 70 and 36 compounds in IPA extractions from the membranes and 13, 12 and 19 from the housings for F1, F2 and F3 respectively. In the hexane extracts, we found 40, 61 and 30 compounds from the membranes and 18, 17 and 15 from the housings (F1, F2 and F3 respectively). In the aqueous extracts, 2, 3 and 2 membrane compounds and 2, 2 and 1 housing compounds were found (F1, F2 and F3 respectively). Among the potentially allergenic compounds from membranes, caprolactam and benzaldehyde were identified. In the housings, methyl methacrylate and styrene were found.

Discussion-Conclusion
This study highlights the presence of potentially immuno-allergic compounds in in-line filters used for the infusion of injectable chemotherapy preparations, which could potentially migrate in contact with them. Although obtained under exaggerated conditions, these results support the hypothesis of a container-content interaction between the filter and some preparations, likely to compromise patient safety. This underlines the importance of assessing container-content interactions for the devices used in chemotherapy reconstitution units and chemotherapy administration, in order to ensure the safety of preparations.

Key words: Filtration - Antineoplastic agents - Hypersensitivity