Mimicking in vivo phase 1 metabolism of pharmaceuticals by Electrochemistry

Breman, Annemay Carolien (2022) Mimicking in vivo phase 1 metabolism of pharmaceuticals by Electrochemistry. Bachelor's Project, Pharmacy.

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Abstract

Early assessment of phase 1 metabolic pathways can help to identify in vivo metabolites, thereby giving an insight in which drug candidates to eliminate before entering a loathsome clinical trial. The aim of this study was to investigate whether electrochemistry (EC) coupled off-line with liquid chromatography combined with mass spectrometry (LC-MS) is competent to mimic in vivo phase 1 metabolism of pharmaceuticals. With the aim of doing this, several pharmaceuticals were oxidized in an electrochemical cell under various conditions followed by detection by LC/MS to look whether known in vivo oxidative metabolites were formed. In the present study, fifteen distinctive pharmaceuticals were used as drug compounds to study the formation of potential in vivo phase 1 metabolites. The in vivo phase 1 metabolism of seven pharmaceuticals was successfully mimicked whereas this was not the case for six other pharmaceuticals. For the last two pharmaceuticals, only one of the two expected oxidative metabolites was detected. The catalytic working of hydrogen peroxide combined with a platinum electrode was found to have a major effect on oxygen-insertion reactions and thereby on hydroxylation, N-oxidation and sulfoxidation. Whereas the cell potential did not have a significant influence on the metabolite formation.

Item Type:	Thesis (Bachelor's Project)
Supervisor name:	Permentier, H.P.
Degree programme:	Pharmacy
Thesis type:	Bachelor's Project
Language:	English
Date Deposited:	24 Jun 2022 10:52
Last Modified:	24 Jun 2022 10:52
URI:	https://fse.studenttheses.ub.rug.nl/id/eprint/27366

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