Optimization of a forced degradation study of atorvastatin employing an experimental design approach

Authors

  • Maja Hadzieva Gigovska Research & Development, ALKALOID AD, Blvd. Aleksandar Makedonski 12, 1000 Skopje, R. Macedonia Faculty of Pharmacy, University “Ss Cyril and Methodius”, Mother Theresa 47, 1000 Skopje, R. Macedonia
  • Ana Petkovska Alkaloid AD, Skopje Blvd. Aleksandar Makedonski 12 1000 Skopje, Macedonia
  • Jelena Acevska Faculty of Pharmacy University Ss.Cyril and Methodius Mother Tereza 47 1000 Skopje, POB 36
  • Natalija Nakov Faculty of Pharmacy University Ss.Cyril and Methodius Mother Tereza 47 1000 Skopje, POB 36
  • Blagica Manchevska Alkaloid AD, Skopje Blvd. Aleksandar Makedonski 12 1000 Skopje, Macedonia
  • Packa Antovska Alkaloid AD, Skopje Blvd. Aleksandar Makedonski 12 1000 Skopje, Macedonia
  • Sonja Ugarkovic Research & Development, ALKALOID AD, Blvd. Aleksandar Makedonski 12, 1000 Skopje, R. Macedonia
  • Aneta Dimitrovska Faculty of Pharmacy, University “Ss Cyril and Methodius”, Mother Theresa 47, 1000 Skopje, R. Macedonia

DOI:

https://doi.org/10.20450/mjcce.2018.1471

Keywords:

Atorvastatin, related and degradation products, LC/MS, experimental design, forced degradation

Abstract

This study involved the optimization of experimental conditions for the forced degradation of atorvastatin employing the experimental design (DoE) approach, as a scientific multifactorial strategy. Using 2n full factorial design, stress conditions of oxidative, hydrolytic and thermal degradation were optimized to obtain a targeted level of atorvastatin degradation. Atorvastatin and all related and degradation products were separated on Poroshell 120 EC C18 50 ´ 3.0 mm 2.7 μm, using 10 mM ammonium formate and acetonitrile as mobile phases in the gradient mode. The impurity structures were confirmed by the direct hyphenation of a liquid chromatograph to an ion trap mass spectrometer with a heated electrospray ionization interface.

This study highlights the multifold benefits of implementing the DoE concept, which provides a better understanding of the significant factors responsible for degradation and ensures a successful way to achieve degradation, thereby replacing the trial and error approach used in conventional forced degradation studies.

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Published

2018-11-15

How to Cite

Hadzieva Gigovska, M., Petkovska, A., Acevska, J., Nakov, N., Manchevska, B., Antovska, P., Ugarkovic, S., & Dimitrovska, A. (2018). Optimization of a forced degradation study of atorvastatin employing an experimental design approach. Macedonian Journal of Chemistry and Chemical Engineering, 37(2), 111–125. https://doi.org/10.20450/mjcce.2018.1471

Issue

Vol. 37 No. 2 (2018)

Section

Analytical Chemistry

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