Evidence of free radical generation from the interaction of polyethylene glycol with PVC medical tubing

Abstract

The combination of polyethylene glycol (PEG) and polyvinyl chloride (PVC) medical tubing was previously demonstrated to degrade an active pharmaceutical ingredient (API), a phenomenon proposed to occur by free radical mechanisms. This study tests the hypothesis that dehydrochlorinated PVC at the tubing surface increases the oxidative potential of PEG autooxidation via radical propagation. The functional group composition at the surfaces of intact, autoclaved, or force-degraded medical grade PVC tubings was assessed by attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR). The content of double bonds in PVC was correlated with the extent of API degradation in the PEG–PVC system, with the repeated autoclaving cycle treatments yielding the most reactive tubing. After PEG exposure, new functional groups on the surface of PVC were observed, indicating the participation of PVC in the oxidation reactions. The PEG–PVC system was further probed by the fluorinated spin-trap reagent FDMPO, where trapped adducts were analyzed by 19F NMR, revealing the presence of three radical species. Trapped adducts were then analyzed by two-dimensional liquid chromatography tandem mass spectrometry (2D-LC-MS/MS), which revealed the presence of free chlorine atoms and/or hypochlorous acid and a PEG alkoxy radical. Chemical mechanisms describing the interaction between dehydrochlorinated PVC and PEG are proposed to explain the presence of free radicals and the functional group changes in the PVC surface.