Stability of dacarbazine in amber glass vials and polyvinyl chloride bags

Abstract

The stability of dacarbazine in commercial glass vials and polyvinyl chloride (PVC) bags in various storage conditions and the emergence of 2-azahypoxanthine, a major degradation product possibly linked with some adverse effects, were studied. Triplicate samples of reconstituted (11 mg/mL) and diluted (1.40 mg/mL) dacarbazine admixtures were prepared and stored at 4 degrees C or at 25 degrees C in daylight, fluorescent light, or the dark. The effect of several light-protective measures (amber glass vials, aluminum foil wrapping, and opaque tubing) on dacarbazine stability in a simulated i.v. infusion system was also evaluated. Dacarbazine quantification and main degradation product determination were performed by high-performance liquid chromatography. Stability was defined as conservation of 90-105% of initial dacarbazine concentration without major variations in clarity, color, or pH and without precipitate formation. Reconstituted dacarbazine solutions were stable for 24 hours at room temperature and during light exposure and stable for at least 96 hours at 2-6 degrees C when stored in the dark. After dilution in PVC bags, stability time increased from 2 hours in daylight to 24 hours in fluorescent light and to 72 hours when covered with aluminum foil. After two hours of simulated infusion, dacarbazine remained stable. Diluted dacarbazine solutions stored at 2-6 degrees C were stable for at least 168 hours. The only degradation product found was 2-azahypoxanthine, which was detected in every sample. The storage and handling of dacarbazine should take into account both the loss of the drug and the production of its potentially toxic degradation product. Dacarbazine must be carefully protected from light, administered using opaque infusion tubing, and, if necessary, refrigerated before administration to reduce 2-azahypoxanthine formation.