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Belgrade, Serbia

Malenovic A.,Institute of Drug Analysis | Jancic-Stojanovic B.,Institute of Drug Analysis | Ivanovic D.,Institute of Drug Analysis | Medenica M.,Serbian Institute of Chemistry
Journal of Liquid Chromatography and Related Technologies | Year: 2010

In this paper, the definition of simvastatin degradation profile by microemulsion liquid chromatography (MELC) is presented. The aim of the study was to investigate simvastatin stability after various stress tests, such as: acid and base hydrolysis, oxidation, and heat. The kinetics of acid and oxidative degradation was also studied. The complex retention mechanism occurring when microemulsion is used as eluent enabled the successful separation of a large number of degradants in prepared stress samples. The existence of a second partitioning site due to microstructural and interfacial characteristics of o/w microemulsion eluent facilitated HPLC separation. All the expected capabilities of MELC method were realized, demonstrating the advantage and value of the MELC method for a wide area of pharmaceutical analysis. For acid degradation the second order rate constant and half-life were calculated. Oxidative decomposition proved to be the first order reaction for which the rate constant and half-life were also determined.


Maskovic M.,Medicines and Medical Devices Agency of Serbia | Jancic-Stojanovic B.,Institute of Drug Analysis | Malenovic A.,Institute of Drug Analysis | Ivanovic D.,Institute of Drug Analysis | Medenica M.,Serbian Institute of Chemistry
Acta Chromatographica | Year: 2010

Robustness testing is an important part of method validation. Many ideas on robustness testing can be found in the literature, but the most useful approach is application of experimental design. In the work discussed in this paper, Plackett-Burman design was used for robustness testing of an LC method. Robustness was assessed for a previously validated method developed for chromatographic analysis of perindopril tert -butylamine and its impurities. Eleven factors (seven real and four dummies) in twelve experiments were examined. Robustness was assessed by graphical (half-normal probability plots and Pareto charts) and statistical ( t -test) methods. For estimation of the standard error of effect (necessary for t -test estimation) calculations based on negligible effects and Dong's algorithm were used at the significance levels α = 0.05 and α = 0.01. In this way the effect of the factors was completely defined and, furthermore, nonsignificant intervals for significant variables were calculated. Finally, on the basis of the worst-case situation, system-suitability tests were performed and acceptance limits for certain values were calculated.

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