Stability of Cabazitaxel Solution after Dilution in Normal Saline and Stored in Glass

Abstract

Objective: To evaluate the stability of cabazitaxel diluted in 0.9% sodium chloride (NS) and stored in glass. Methods: A reverse-phase stability-indicating liquid chromatographic method was developed and validated before the study. The commercially available product was prepared according to the manufacturer's instructions, and further diluted in NS to obtain concentrations of 0.120 mg/mL and 0.240 mg/mL cabazitaxel and stored in glass under refrigeration and at 25ºC, all of them protected from light. The concentration of cabazitaxel was evaluated over a period of 21 days. Results: Physical stability: The visual inspection of the stored samples to 25ºC (0.120 mg/mL and 0.240 mg/mL) indicated appearance of a white precipitate in both cases on the day 2 of study. In the case of the refrigerated samples, a similar precipitate appears on the day 6 of the study for the 0.240 mg/mL concentration and on the day 21 for 0.120 mg/mL concentration. Chemical stability: The samples that stay physically stable have been evaluated by HPLC method obtaining in all determinations a remaining percentage >95%. Solutions of cabazitaxel were subjected to a forced degradation analysis. Conclusion: Solutions of cabazitaxel 0.120 mg/mL prepared in NS and stored in glass retained more than 95% of the initial drug concentration when stored for one day at 25ºC and for twenty days at 4ºC. Solutions of cabazitaxel 0.240 mg/mL prepared in the same conditions retained more than 95% of the initial drug concentration when stored for one day at 25ºC and for two days at 4ºC.

Stability study of concentrate-solvent mixture & infusion solutions of Jevtana® cabazitaxel for extended multi-dosing

“…12 The stability in the form of concentration measurement for infusion solution stored in glass bottles has been examined previously as well. 11 The results demonstrate that the cabazitaxel maintains its stability from a physical and chemical point of view for up to 2 weeks after the concentrate-solvent mixture prepared and/or infusion solution is prepared for all storage conditions. However, since the SmPC states that cabazitaxel cannot be stored over 30 C, 2 the 40 C should not be re-used.…”

“…Degradation products have been separated by other research groups, however, not been identified. [8][9][10][11] A thorough degradation study with another cabazitaxel taxane derivate DS80100717 has also been conducted. 12 The stability in the form of concentration measurement for infusion solution stored in glass bottles has been examined previously as well.…”

“…12 The stability in the form of concentration measurement for infusion solution stored in glass bottles has been examined previously as well. 11…”