| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Mielczarek, Przemyslaw Kotlinska, Jolanta H. Smoluch, Marek Gotszalk, Teodor Labuz, Krzysztof Silberring, Jerzy Babij, Michal Suder, Piotr |
| Spatial Coverage |
Netherlands |
| Description |
Country affiliation: Poland Author Affiliation: Mielczarek P ( AGH University of Science and Technology, Faculty of Materials Science and Ceramics, Department of Biochemistry and Neurobiology, Mickiewicza 30, 30-059 Krakow, Poland); Smoluch M ( AGH University of Science and Technology, Faculty of Materials Science and Ceramics, Department of Biochemistry and Neurobiology, Mickiewicza 30, 30-059 Krakow, Poland.); Kotlinska JH ( Department of Pharmacology and Pharmacodynamics, Medical University, Chodzki 4a, 20-093 Lublin, Poland.); Labuz K ( The Rydygier Hospital in Krakow, Addiction Outpatient Clinic, os. Zlotej Jesieni 1, 31-869 Krakow, Poland.); Gotszalk T ( Faculty of Microsystem Electronics and Photonics, Wroclaw University of Technology, Janiszewskiego 11/17, 50-372 Wroclaw, Poland.); Babij M ( Faculty of Microsystem Electronics and Photonics, Wroclaw University of Technology, Janiszewskiego 11/17, 50-372 Wroclaw, Poland.); Suder P ( AGH University of Science and Technology, Faculty of Materials Science and Ceramics, Department of Biochemistry and Neurobiology, Mickiewicza 30, 30-059 Krakow, Poland); Silberring J ( AGH University of Science and Technology, Faculty of Materials Science and Ceramics, Department of Biochemistry and Neurobiology, Mickiewicza 30, 30-059 Krakow, Poland) |
| Abstract |
The metabolic pathways of selegiline (a drug used for the treatment of early-stage Parkinson's disease) were analyzed by electrochemical oxidation with application of the flow electrochemical cell consisting of three electrodes (ROXY™, Antec, the Netherlands). Two types of working electrodes were applied: glassy carbon (GC) and boron-doped diamond (BDD). The potential applied at working electrode and composition of the solvent were optimized for the best conditions for oxidation and identification processes. All products were directly analyzed on-line by mass spectrometry. For further characterization of electrochemical oxidation products, the novel approach involving reversed phase chromatography linked to mass spectrometry with dielectric barrier discharge ionization (DBDI-MS) was used. In this manuscript, we report a novel technique for simulation of drug metabolism by electrochemical system (EC) connected to liquid chromatography (LC) and dielectric barrier discharge ionization (DBDI) mass spectrometry (MS) for direct on-line detection of electrochemical oxidation products. Here, we linked LC/DBDI-MS system with an electrochemical flow cell in order to study metabolic pathways via identification of drug metabolites generated electrochemically. The DBDI source has never been used before for identification of psychoactive metabolites generated in an electrochemical flow cell. Our knowledge on the biological background of xenobiotics metabolism and its influence on human body is constantly increasing, but still many mechanisms are not explained. Nowadays, metabolism of pharmaceuticals is mainly studied using liver cells prepared from animals or humans. Cytochrome P450, present in microsomes, is primarily responsible for oxidative metabolism of xenobiotics. It was also shown, that breakdown of popular medicines may be successfully simulated by electrochemistry under appropriate conditions. The presented experiments allow for comparison of these two entirely distinct techniques using selegiline as the model xenobiotic with well-described metabolic pathway in human body. The obtained results for selegiline oxidation show that it is possible to generate the most important selegiline metabolites present in human body - some of them with psychoactive properties, such as methamphetamine and amphetamine. These metabolites, serving as an evidence of the xenobiotic intake, can also be produced, among a larger group of metabolites, by incubation of selegiline with rat and human liver microsomes. The EC/LC/DBDI-MS system provides novel, promising platform for drugs screening of the phase I metabolism. The metabolites can be detected directly by MS or collected and separated by liquid chromatography. |
| ISSN |
00219673 |
| Volume Number |
1389 |
| e-ISSN |
18733778 |
| Journal |
Journal of Chromatography A |
| Language |
English |
| Publisher |
Elsevier |
| Publisher Date |
2015-04-10 |
| Publisher Place |
Netherlands |
| Access Restriction |
One Nation One Subscription (ONOS) |
| Subject Keyword |
Chemistry Techniques, Analytical Methods Electrochemistry Mass Spectrometry Selegiline Chemistry Metabolism Amphetamines Analysis Animals Cells, Cultured Instrumentation Chromatography, Liquid Cytochrome P-450 Enzyme System Electrodes Humans Microsomes, Liver Netherlands Oxidation-reduction Rats Journal Article Research Support, Non-u.s. Gov't Discipline Analytical Chemistry |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Organic Chemistry Medicine Analytical Chemistry Biochemistry |
