Metabolic studies of tetrazepam based on electrochemical simulation in comparison to in vivo and in vitro methods
| Autor: | Wiebke Lohmann, Anne Baumann, Herbert Oberacher, Uwe Karst, Birthe Schubert |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Metabolite
Hydroxylation Tandem mass spectrometry Online Systems Biochemistry Analytical Chemistry Electrochemical cell Benzodiazepines chemistry.chemical_compound Tandem Mass Spectrometry In vivo Tetrazepam Liquid chromatography–mass spectrometry Microsomes medicine Humans Electrodes Diazepam Chromatography Muscle Relaxants Central Organic Chemistry Electrochemical Techniques General Medicine Metabolic pathway chemistry Chromatography Liquid medicine.drug |
| Zdroj: | Journal of Chromatography A. 1216:3192-3198 |
| ISSN: | 0021-9673 |
| DOI: | 10.1016/j.chroma.2009.02.001 |
| Popis: | During the last 2 years, the knowledge on the metabolic pathway of tetrazepam, a muscle relaxant drug, was expanded by the fact that diazepam was identified as a degradation product of tetrazepam. The present study demonstrates that this metabolic conversion, recently discovered by in vivo studies, can also be predicted on the basis of a purely instrumental method, consisting of an electrochemical cell (EC) coupled to online liquid chromatography (LC) and mass spectrometry (MS). By implementing a new electrochemical cell type into the EC-LC–MS set-up and by an enhanced oxidation potential range up to 2 V, one limitation of the electrochemical metabolism simulation, the hydroxylation of alkanes and alkenes, has been overcome. Instead of commonly used flow-through cell with a porous glassy carbon working electrode, a wall-jet cell with exchangeable electrode material was used for this study. Thereby, the entire metabolic pathway of tetrazepam, in particular including the hydroxylation of the tetrazepam cyclohexenyl moiety, was simulated. The electrochemical results were not only compared to microsomal incubations, but also to in vivo experiments, by analysing urine samples from a patient after tetrazepam delivery. For structure elucidation of the detected metabolites, MS/MS experiments were performed. The comparison of electrochemistry to in vitro as well as to in vivo experiments underlines the high potential of electrochemistry as a fast screening tool in the prediction of metabolic transformations in drug development. |
| Databáze: | OpenAIRE |
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