Degradation of paracetamol and other constituents in Perfalgan®

Abstract

Background: The manufacturers of Perfalgan^®, a formulation of intravenous paracetamol, recommend that each ampoule be used once only. This is most likely due to concerns regarding degradation of paracetamol or other ingredients in the solution, and sterility issues. However, in South Africa, where the expense of this drug limits use, some centres use one ampoule for multiple paediatric cases over the course of 12–24 hours. No obvious clinical adverse effects have been reported.
Aim: The aim of this study was to examine this practice by assessing drug bioavailability as well as the in vitro stability of the paracetamol and excipients in Perfalgan^® on exposure to air and specific stressors over time.
Methodology: High-performance liquid chromatography (HPCL-UV) was used to determine the concentration of paracetamol and the presence of degradation products in samples taken at set time intervals following exposure of Perfalgan^® to air and stressors. Since changes in other components, or excipients, may impact efficacy, these were measured using nuclear magnetic resonance (1H NMR). The octanol:water partition coefficient was used as an indicator of bioavailability. Ultraviolet spectroscopy was used to calculate the penetration of paracetamol in Perfalgan^® into the lipid layer.
Results: The paracetamol in Perfalgan^® did not degrade on exposure to air over 24 hours. Neither did it degrade on exposure to acid, alkali, oxidative or heat stress. 1H NMR revealed no change in the formulation of Perfalgan^® except for the conversion of the oxygen scavenger cysteine to cystine. The octanol:water partition coefficient likewise stayed constant and was in agreement with the value of 0.46–0.49 quoted in the literature.
Conclusion: Paracetamol and the excipients in Perfalgan^® did not degrade on exposure to air and other stressors over 24 hours. The drug retained its lipid permeability over this period.