Multidisciplinary Approach to Deciphering Etoposide Infusion Reactions and Potential Role of Polyethersulfone Filter Membranes

Abstract

PURPOSE Etoposide, a topoisomerase II inhibitor used clinically to treat cancer, has been associated with severe anaphylactic infusion related adverse drug reactions (ADRs). In a previous study we identified a hydrophilic polyethersulfone filter as a possible cause of increased rates of pediatric etoposide infusion reactions. In this multidisciplinary follow-up analytical study, we aimed to assess the chemical structure of etoposide after passing through the same hydrophilic polyethersulfone filter. METHODS An etoposide 0.4 mg/mL infusion was prepared under aseptic conditions and then passed through a standard IV infusion set with an in-line filter in place. Samples were taken in triplicate using a needle-less access system to include sampling sites directly from the IV bag port and from the IV tubing both before and after the in-line filter. Samples were diluted into mobile phase, then an aliquot was injected into a high-performance liquid chromatography mass spectrometry HPLC-MS (Thermo TSQ Quantum Ultra) system coupled to a Diode Array Detector (DAD) (Thermo Dionex Ultimate 3000). Etoposide was monitored using a selected reaction monitoring scan (SRM) of 606.2/228.8 and wavelengths of 210, 220, 254, and 280 nm for 30 minutes. RESULTS No detectable differences were observed upon comparing the three samples. Based on these results, a chemical change in etoposide resulting from an in-line filter is unlikely to be the primary cause of increased rates of infusion reactions. CONCLUSION Pharmacists working in healthcare systems, observe many ADRs, but rarely have the resources necessary to investigate the potential etiology or causality. This report highlights importance of multi-disciplinary collaboration to investigate serious ADRs.