Stability of Bortezomib Reconstituted with 0.9% Sodium Chloride at 4 degrees C and Room Temperature (23 degrees C)

Background: The bortezomib product monograph indicates that after reconstitution, the drug may be stored for up to 3 h in a syringe, and the total storage time for the reconstituted material must not exceed 8 h when exposed to normal indoor lighting. Given the product packaging and vial size, as well as the currently recommended dosage regimen (which, for a clinic treating between 1 and 10 patients daily, entails using about half a vial each day), there is potential for substantial wastage, about $13,000 for a 5-cycle course of bortezomib therapy for a single patient. The aim of this study was to evaluate the stability of bortezomib (3.5-mg vials) reconstituted with 3.5 mL of 0.9% sodium chloride (NS) to produce a 1 mg/mL solution. Methods: On study day 0, six 3.5-mg vials of bortezomib were reconstituted with 3.5 mL NS per vial, to prepare solutions of 1.0 mg/mL. Three of the vials were stored in the refrigerator, and 3 were stored at room temperature. Concentration was measured and physical inspection was completed for each vial on study days 0, 1, 4, 8, 11, 15, 18, 21, 28, 34, and 42. The intervals between study days were consistent with the recommended dosage regimen, as published in the product monograph. Bortezomib concentrations were determined by a validated, stability-indicating, liquid chromatographic method. Results: All solutions remained clear and colourless. During the study period, all solutions retained more than 98% of the initial concentration, and the amount remaining on day 42 was greater than 98% (with 95% confidence). During the study period, the absolute deviation from the known concentration for standards and quality control samples averaged less than 4%, and analytical reproducibility within a day (by coefficient of variation) was high, with error on replicate analysis averaging less than 2%. Conclusions: Bortezomib, supplied in 3.5-mg vials and reconstituted with 3.5 mL NS, is physically and chemically stable for up to 42 days at 4 degrees C or at room temperature.