Stability study of fotemustine in PVC infusion bags and sets under variousconditions using a stability-indicating high-performance liquid chromatographic assay

The stability and compatibility of fotemustine, a nitrosourea anticancer ag ent, in 5% dextrose solution with polyvinyl chloride (PVC) containers and a dministration sets were studied under different conditions of temperature a nd light. The drug was diluted to 0.8 and 2 mg ml(-1) in 100 or 250 mi 5% d extrose injection solutions for l-h simulated infusions using PVC bags and administration sets with protection from light. After preparation in the PV C bags containing 5% dextrose, fotemustine was also prepared at the same co ncentrations and stored at 4 degrees C for 48 h and at room temperature (22 degrees C) or at sunray exposure(> 30 degrees C) over 8 h with or without protection from light. The solution samples were removed immediately at var ious time points of simulated infusions and storage, and stored at - 20 deg rees C until analysis. The physical compatibility with PVC and chemical sta bility in solution of fotemustine were assessed by visual examination and b y measuring the concentration bf the drug in duplicate using a stability-in dicating high-performance chromatographic assay. When admired with a 5% dex trose solution, fotemustine 2 and 0.8 mg ml(-1) was compatible and stable o ver 1-h of simulated infusion using PVC bags through PVC administration set s with protection from light. On the other hand, in the same diluent, fotem ustine was compatible and stable with PVC bags for at least 8 h at 22 degre es C with protection from light and for at least 48 h at 4 degrees C with p rotection from light. There were no pH variation, no visual change, no colo r change, no visible precipitation and no loss of the drug. Conversely, whe n the solutions were exposed to light (ambient or solar), the drug concentr ation decreased rapidly, leading to the production of a degradation product as shown by mass spectral analysis and a discoloration of the solutions. F inally, in all cases, no DEHP (di-2-ethylhexyl phthalate) was detected in t he injection solution. (C) 1998 Elsevier Science B.V. All rights reserved.