Stability, compatibility and plasticizer extraction of quinine injection added to infusion solutions and stored in polyvinyl chloride (PVC) containers

Abstract

The stability of quinine was determined in various diluents and in polyvinyl chloride (PVC) containers. The release of diethyhexyl phthalate (DEHP) from PVC bags into intravenous infusions of quinine was also measured. We used an injection of two doses of quinine; quiniforme at 500 mg and quinimax at 400 mg in either 250- or 500-ml PVC infusion bags containing 5% dextrose, to give initial nominal concentrations of 2 or 1 mg ml −1 quiniforme and 1.6 or 0.8 mg ml −1 quinimax, the mean concentrations commonly used in clinical practice. Samples were assayed by stability-indicating high-performance liquid chromatography (HPLC) and the clarity was determined visually. Experiments were conducted to determine whether the stability and compatibility of quinine would be compromised, and whether DEHP would be leached from PVC bags and PVC administration sets during storage and simulated infusion. There was no substantial loss of quiniforme and quinimax over 1- or 2-h simulated infusion irrespective of the diluent, and storage during 8 h at 22°C, 48 or 72 h at 4°C and 96 h at 45°C. Leaching of DEHP was also detected during simulated infusion delivery using PVC bags and PVC administration sets. The quantity was less than 2 μg ml −1. During storage at 4°C and room temperature the leaching of DEHP was low, but when the temperature was 45°C the quantity was high, 21 μg ml −1. To minimise patient exposure to DEHP, quinine solutions with all drugs should be infused immediately or stored for a maximum of 48 h at 4°C.