PP-003 Stability study of bortezomib (velcade) with limit test for all degradation products

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Abstract

Background

Bortezomib (Velcade) is a cytostatic drug used for the treatment of several cancer types. The drug must be reconstituted before administration and the reconstituted solution is stable for 8 hours according to the manufacturer. Leftovers therefore cannot be used on subsequent days. Since one vial of Velcade costs approximately €1000, this imposes a significant economic loss for hospital budgets. Several studies have shown that the reconstituted drug is stable for > 24 hours, but none of these have contained identification and quantification of the degradation products (DPs) formed during storage.

Purpose

To conduct a stability study of reconstituted Velcade in the manufacturer’s vial with quantification and identification of all DPs.

Material and methods

The analytical method was based on the work of Srinivasulu and colleagues,1 and validated according to ICH regulations. The storage conditions were 5°C±3°C, protected from light, and the study consisted of the following measurements: assay, DPs and visual inspection. Measurements were conducted at 0, 1, 3, 7, 10 and 14 days. The acceptance criteria for the study were: assay 95–105% of initial value, bortezomib impurity E <3.0%, other impurities <0.5%, summarised other impurities <2.0% and a clear liquid.

Results

The solution was clear and colourless throughout the study. Only low amounts of DPs were observed, and no change during the study. However, due to a large SD related to the low sampling volume and viscosity of the solution, the 95% CI of the assay measurement exceeded 105% after 13 days, thus limiting the stability of the solution to 12 days. The increased shelf-life has since been implemented at our hospital pharmacy and led to a cost reduction of approximately €135 000.

Conclusion

The stability of reconstituted Velcade in the manufacturer vial was at least 12 days at 5°C±3 °C, protected from light.

References and/or acknowledgements

7. Srinivasulu K, et al. Development and validation of a stability indicating LC method for the assay and related substances determination of a proteasome inhibitor bortezomib. Chromatogr Res Int2012: article ID801720, 13 pages.

References and/or acknowledgements

No conflict of interest

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