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Current Pharmaceutical Analysis

Author(s): Hedvig Arnamo*, Michel J.X. Hillebrand , Alwin D.R. Huitema , Bastiaan Nuijen , Hilde Rosing and Jos H. Beijnen

DOI: 10.2174/1573412916666200327144051

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

Page: [691 - 701] Pages: 11

  • * (Excluding Mailing and Handling)

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 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: 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.

Conclusion: As an addition, the only naturally occurring degradation product found has been identified and a degradation reaction has been suggested.

Keywords: Cabazitaxel, high-performance liquid chromatography, mass spectrometry, stability, left-over, degradation.

Graphical Abstract

[1]
European Medicines Agency (EMA). Assessment Report For Jevtana Procedure No.: EMEA / H / C /002018. Committee for Medicinal Products for Human Use; CHMP: Canary Wharf, United Kingdom, 2011.
[2]
JEVTANA® - Summary of Product Characteristics (SmPC). Published, 2011. Last Updated 2017. Available at http://Ema.Europa.Eu. (Accessed on: October, 2018)..
[3]
Villanueva, C.; Bazan, F.; Kim, S.; Demarchi, M.; Chaigneau, L.; Thiery-Vuillemin, A.; Nguyen, T.; Cals, L.; Dobi, E.; Pivot, X. Cabazitaxel: a novel microtubule inhibitor. Drugs, 2011, 71(10), 1251-1258.
[http://dx.doi.org/10.2165/11591390-000000000-00000] [PMID: 21770474]
[4]
Venkatesh, B.; Mathrusri Annapurna, M.; Pramadvara, K. Analytical stress degradation studies of cabazitaxel (a semi synthetic natural taxoid) using liquid chromatography. Pharm. Methods, 2015, 6(3), 137-142.
[http://dx.doi.org/10.5530/phm.2015.6.21]
[5]
Sawicki, E.; Beijnen, J.H.; Schellens, J.H.M.; Nuijen, B. Pharmaceutical development of an oral tablet formulation containing a spray dried amorphous solid dispersion of docetaxel or paclitaxel. Int. J. Pharm., 2016, 511(2), 765-773.
[http://dx.doi.org/10.1016/j.ijpharm.2016.07.068] [PMID: 27480397]
[6]
Moes, J.J.; Koolen, S.L.; Huitema, A.D.; Schellens, J.H.M.; Beijnen, J.H.; Nuijen, B. Pharmaceutical development and preliminary clinical testing of an oral solid dispersion formulation of docetaxel (ModraDoc001). Int. J. Pharm., 2011, 420(2), 244-250.
[http://dx.doi.org/10.1016/j.ijpharm.2011.08.041] [PMID: 21907780]
[7]
Rajan, N.; Basha, A.K. Validated stability indicating UPLC method for simultaneous determination of assay, related substances, and degradation products of cabazitaxel drug substance and its pharmaceutical injection forms. J. Pharmaceut. Sci. Res., 2014, 6(12), 411-419.
[8]
Li, C.; Lan, G.; Jiang, J.; Sun, M.; Hang, T. Development and validation of a stability-indicating HPLC method for the determination of the impurities in cabazitaxel. Chromatographia, 2015, 78, 825-831.
[http://dx.doi.org/10.1007/s10337-015-2900-4]
[9]
Official Monographs - Paclitaxel. USP 35, 2012, 100, 4195-4197.
[10]
ICH, Guideline Q1A(R2) Stability Testing of New Drug Substances and Products. International Conference on Harmonization, 2003, p. 24.
[11]
ICH Topic Q2(R1) Validation of Analytical Procedures Text and Methodology. International Conference on Harmonization, 2005, p. 17.
[12]
ICH Topic Q1(B) Stability Testing: Photostability Testing of New Drug Substances and Products Q1B. International Conference on Harmonization, 2003, p. 24.
[13]
María, E.B.; Fuensanta, S.R.; Catalina, B.O. Stability of cabazitaxel solution after dilution in normal saline and stored in glass. Indian J. Pharmaceut. Edu. Res., 2015, 49(1), 40-45.
[http://dx.doi.org/10.5530/jper.49.1.6]
[14]
Shao, Y.; Zhang, C.; Yao, Q.; Wang, Y.; Tian, B.; Tang, X.; Wang, Y. Improving cabazitaxel chemical stability in parenteral lipid emulsions using cholesterol. Eur. J. Pharm. Sci., 2014, 52, 1-11.
[http://dx.doi.org/10.1016/j.ejps.2013.09.024] [PMID: 24153395]