Přehled

Project summary 

Active pharmaceutical ingredients in drug products can undergo degradation during their long-term storage which can lead to loss of their pharmacological effect or even to adverse effects on human health. One of the most common degradation processes is oxidation, which is usually initiated by radicals, mediated by peroxides, or by electron transfer to metal ions. Stability testing is thus one of the key steps in the development of safe and effective drug products.

In our previous studies, we have reported on the benefits of using an electrochemical approach to degradation studies of pharmaceuticals [1]. The aim of this project is a development of an innovative methodology of forced degradation studies based on the direct connection of the electrochemical reaction cell with LC-MS. Such arrangement will enable better investigation of chemical and electrochemical degradation pathways of active pharmaceutical substances.

The project will be focused in the first phase on the development of an electrochemical cell compatible with LC-MS. The choice of electrode material and degradation conditions has a crucial influence on the composition of the analysis products [2, 3]. Therefore later attention will be paid to the optimization of the electrode material to achieve a suitable composition of degradation products. The final part will compare standard degradation methods with the newly developed methodology.

References

[1] F. Vymyslický, T. Křížek, P. Kozlík, A. Kubíčková, J. Heřt, E. Bartosinska, Alternative method for canagliflozin oxidation analysis using an electrochemical flow cell – Comaparative study, J. Pharm. Biomed. Anal., 207 (2021) 114341. DOI: 10.1016/j.jpba.2021.114341

[2] M. Cindric, M. Vojs, F.M. Matysik, Characterization of the Oxidative Behavior of Cyclic Nucleotides Using Electrochemistry–Mass Spectrometry, Electroanalysis, 27 (2015) 234. DOI: 10.1002/elan.201400414

[3] E. Bartosinska, P. Kozlík, A. Kubíčková, J. Heřt, J. Fischer, T. Křížek, Comparison of static and dynamic mode in the electrochemical oxidation of fesoterodine with the use of experimental design approach Talanta, 226 (2021), 122141. DOI: 10.1016/j.talanta.2021.122141

Expected skills of the applicant: MSc. or equivalent in Chemistry (required); experience in LC/MS and electrochemistry, good knowledge of English.

 

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