Stability of busulfan injection admixtures in 5 % dextrose injection and 0.9% sodium chloride injection

Abstract

Objective. The purpose of this study was to deter mine the stability of busulfan injection at 0.5 and 0.1 mg/mL admixed in 5% dextrose injection and 0.9% sodium chloride injection in PVC and polyolefm bags over 24 hours at 23°C.

Methods. The busulfan injection was prepared by dissolving the bulk powder in a 1:2 mixture of N,N-dimethylacetamide and polyethylene glycol 400 to form a 6 mg/mL solution. The injection was filtered and admixed in the infusion solutions to yield busulfan concentrations of 0.5 and 0.1 mg/mL. Evaluations were performed initially and after 4, 8, and 24 hours of storage for physical and chemical stability. The admix tures were evaluated for physical stability using visual observation in normal light and using a high-intensity monodirectional light beam as well as measuring turbidity. The chemical stability was evaluated by using a stability-indicating HPLC analytical technique.

Results. No physical instabilities were observed. However, busulfan is chemically unstable. At 0.5 mg/mL, potency of at least 95% was retained through 4 hours and at least 90% was retained through 8 hours. After 24 hours, losses of 20% to 30% occurred. At 0.1 mg/mL, drug loss was more rapid. Potency of at least 90% was retained through 4 hours. Losses after 24 hours were about 30% to 40%.

Conclusions. Busulfan injection admixed in 5% dextrose injection or 0.9% sodium chloride injection is unstable. At a concentration of 0.5 mg/mL, ade quate drug delivery is provided within 8 hours of admixture. At the lower concentration of 0.1 mg/mL, adequate drug delivery is only provided for 4 hours.