Stability of Generic Versions of Gemcitabine Hydrochloride Preparation for Injection

Abstract

The anti-tumor agent gemcitabine hydrochloride is stable in solid state; however, deamination occurs in acidic solution, yielding β-uridine analogue, whereas anomerization reaction occurs in basic solution. Thus, the brand-name preparation for injection is supplied as lyophilized dry powder, and ingredients are added to result in acidic solution when dissolved in saline. In this study, a brand- and 6 generic-name medicines were compared with regard to gemcitabine stability, β-uridine production, and pH during storage at 25℃ for 6 months after dissolving in saline. Gemcitabine concentrations were decreased time-dependently, and β-uridine concentrations were increased. The pH values were constant. Another generic medicine supplied as solution was also subjected for comparison. At the start of the experiments (Time 0), β-uridine had already been produced in the generic medicine supplied as solution. These results suggest that the generic medicine supplied as solution has to be maintained for tight control in the processes of manufacturing or distribution.