Stability of 1.0 and 2.5 mg/mL Bortezomib Solution in Vials and Syringes Following Reconstitution with 0.9% Sodium Chloride at 4°C and Room Temperature (23°C)

摘要

Background: Previous publications have demonstrated the stability of l.0mg/mL and 2.5mg/mL of bortezomib for 42 days and 21 days respectively. The introduction of a generic version of bortezomib raised questions of the stability of the generic formulation and the validity of extending stability from one brand to another. Objective: To evaluate the stability of bortezomib 3.5 mg vials reconstituted with 3.5 or 1.4 mL of 0.9% sodium chloride (NS) during storage over 42 days at room temperature and at 40C in syringes and manufacturer vials. Methods: On study day 0, 2.5mg/mL and l.0mg/mL concentrations of the TEVA formulation were prepared. 3 units of each container were stored at room temperature and 3 were stored in the refrigerator. Concentration and physical inspection were completed on study days 0, 1, 3, 7, 10, 14, 22, 28, 34, and 42. Bortezomib concentrations were determined by a validated stability-indicating liquid chromatographic method with UV detection. The recommended beyond-use-date was determined based on the intersection of the lower limit of the 95% confidence interval of the observed degradation rate and the time to achieve 90% of the initial concentration. Results: The analytical method separated degradation products from bortezomib such that the concentration was measured specifically, accurately (deviations from known averaged 2.5%) and reproducibly (replicate error was less than 1% (CV(%)). During the study period all solutions retained more than 95% of the initial concentration in vials and syringes at both temperatures and concentrations. The calculated beyond-use-date exceeded 42 days for all temperatures, concentrations and container combinations. Conclusions: We conclude that 3.5-mg vials of TEVA bortezomib reconstituted with 3.5 mL or 1.4 mL of NS (concentrations of 1.0 and 2.5mg/mL) are physically and chemically stable for at least 42 days at 4°C or room temperature (23°C) in both syringes and the original manufacturer’s glass vials.