Stability study of epirubicin in NaCl 0.9% injection

OBJECTIVE: To determine the stability of epirubicin in NaCl 0.9% injection under hospital storage conditions. METHODS: NaCl 0.9% solution was added to epirubicin lyophilized powder to make a final concentration of 1 mg/mL to study the degradation kinetics and 2 mg/mL to study the stability in polypropylene syringes under hospital conditions. SETTING: Physical chemistry laboratory, Unitat de Fisicoqufmica, Universitat de Barcelona. MAIN OUTCOME MEASURES: Solutions of epirubicin at 2 mg/mL in NaCl 0.9% solutions stored in plastic syringes were studied under hospital conditions at room temperature (25 +/- 1 degrees C) and under refrigeration (4 +/- 1 degrees C) both protected from light and exposed to room light (similar to 50 lumens/m(2)). All samples were studied in triplicate and epirubicin concentrations were obtained periodically throughout each storage/time condition via a specific stability indicating HPLC method. To determine the degradation kinetics,solutions of epirubicin in NaCl 0.9% at 1 mg/mL were stored at different temperatures (40, 50, and 60 degrees C) to obtain the rate degradation constant and the shelf life at room temperature and under refrigeration. RESULTS: The degradation of epirubicin in NaCl 0.9% solutions follows first-order kinetics. The shelf life was defined as the time by which the epirubicin concentration had decreased by 10% from the initial concentration. In this study, epirubicin was stable in NaCl 0.9% injection stored in polypropylene containers for all time periods and all conditions. That results in a shelf life of at least 14 and 180 days at 25 and 4 degrees C, respectively. The maximum decrease in epirubicin concentration observed at 25 degrees C and 14 days was 4%, and at 4 degrees C and 180 days was 8%. The predicted shelf life obtained from the Arrhenius equation was 72.9 +/- 0.2 and 3070 +/- 15 days at 25 and 4 degrees C, respectively. in both dark and illuminated conditions. CONCLUSIONS: Solutions of epirubicin in NaCl 0.9% at 2 mg/mL are chemically stable when they are stored in polypropylene syringes under hospital storage conditions. No special precaution is neccessary to protect epirubicin solutions (2 mg/mL) from light.