Development and Validation of a Stability-indicating HPLC Method for the Analysis of Cabazitaxel in Jevtana® Concentrate-solvent Leftover Samples

Abstract

Aim/Background: In this study, a stability-indicating method of the anticancer agent cabazitaxel was developed and validated. This method will be used to determine the chemical stability of commercially available concentrate-solvent mixture cabazitaxel (Jevtana®) to examine the possibility of multi-dosing from the same product vial after storage. The impossibility to re-use leftovers today is contributing to an unnecessary and significant financial waste. Methods: A forced degradation study of cabazitaxel was performed under different conditions to produce degradation products. Acidic, basic, oxidation, heat, and ultraviolet (UV) light conditions were tested. The method to determine the stability was developed so that potential degradation products would be shown in the UV spectra after separation from cabazitaxel with a C18 column in a high-performance liquid chromatography (HPLC) system. The only degradation product occurring during storage in room temperature and ambient light was identified by accurate mass Orbitrap Mass Spectrometry. Results/Conclusion: A stability-indicating method for cabazitaxel (Jevtana ®) concentrate-solvent mixture has been developed. We demonstrated that this method can be applied to stability studies with the purpose of multi-dosing cabazitaxel from a chemical/physical stability perspective within the tested period of time and conditions. As an addition, the only naturally occurring degradation product found has been identified and a degradation reaction has been suggested.

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

“…However, the stability-indicating capability of the method is the purity determination of the sample as previously concluded, where no other degradation/ impurities are eluting at the same time as cabazitaxel. 4 This was also confirmed with the peak purity in this study. The purity results are here defined as the relative area of cabazitaxel, where the excipient peaks and blanks have been subtracted from the calculation.…”

“…The peaks eluting after cabazitaxel have already been proven to be part of the excipients. 4 No additional peaks, nor any growth or decrease in the peaks were recorded for any of the refrigerated samples concentrate-solvent mixtures (see Figure 1).…”

“…The analytical method used in this study was previously developed and validated at our Institute. 4 In this study, forced degradation samples from the concentrate-solvent mixture together with reference standard cabazitaxel was used to develop a stabilityindicating high-performance liquid chromatography (HPLC) with ultraviolet (UV) and photodiode array (PDA) detection as an assay. The method is validated based on the guidelines from The International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH).…”

“…, Milford Massachusetts, USA)". 4 In this study, the calibration was extended to 750 mg/ml, to adjust for the higher concentrations to be studied in our current investigation. The concentrations of the calibrations were 0, 60, 150, 300, 450, 600 and 750 mg/ml.…”

“…The calibration and quality control were proceeded as and following the requirements of the previous method based on ICH guidelines. [4][5][6][7] Purity was redefined in this study as a relative percentage of the cabazitaxel peak in the sample.…”