An Electrochemical Microfluidic Platform for Human P450 Drug Metabolism Profiling
| Autor: | Ennio Capria, Andrea Fantuzzi, Lok Hang Mak, Gianfranco Gilardi, Stephen P. Collins, Vikash R. Dodhia, Graham Somers, Ejaz Huq, Sheila J. Sadeghi |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Quinidine
Nifedipine Stereochemistry NANODEVICES Microfluidics Electrochemistry Substrate Specificity Analytical Chemistry chemistry.chemical_compound Cytochrome P-450 Enzyme System Monolayer medicine Humans Methyl methacrylate Electrodes Chromatography Chemistry Electrochemical Techniques ELECTRODE SYSTEMS Ondansetron HUMAN P450 MICROFLUIDICS Electrode Microsomes Liver Titration Drug metabolism Carbolines medicine.drug |
| Zdroj: | Analytical Chemistry. 82:10222-10227 |
| ISSN: | 1520-6882 0003-2700 |
| DOI: | 10.1021/ac102480k |
| Popis: | This paper is the first report of a P450-electrode in a microfluidic format. A 30 μL microfluidic cell was made in poly(methyl methacrylate) containing the inlet, outlet, and reaction chamber with two electrode strips, one of which contains the human cytochrome P450 3A4 covalently bound to gold via a 6-hexanethiol and 7-mercaptoheptanoic acid (1:1) self-assembled monolayer. The electrochemical response of the P450-electrode in the microfluidic cell was tested using four drugs that are known substrates of P450 3A4: quinidine, nifedipine, alosetron and ondansetron. Titration experiments allowed the electrochemical measurements of K(M) for the four drugs, with values of 2.9, 29.1, 113.4, and 114.1 mM, respectively. The K(M) values are found to be in good agreement and correctly ranked with respect to the published literature on human liver microsomes and baculosomes: [ondansetron ≈ alosetronnifedipinequinidine]. The results presented in this paper represent a step forward for a rapid evaluation of the interaction of P450 and drug, requiring small volumes of new chemical entities to be tested. |
| Databáze: | OpenAIRE |
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