Macedonian Journal of Chemistry and Chemical Engineering (Nov 2018)

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

  • Maja Hadzieva Gigovska,
  • Ana Petkovska,
  • Jelena Acevska,
  • Natalija Nakov,
  • Blagica Manchevska,
  • Packa Antovska,
  • Sonja Ugarkovic,
  • Aneta Dimitrovska

DOI
https://doi.org/10.20450/mjcce.2018.1471
Journal volume & issue
Vol. 37, no. 2
pp. 111 – 125

Abstract

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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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