Bioanalytické metodické přístupy při sledování osudu nového potenciálního léčiva v organismu pomocí HPLC-PDA-MS-MS
Bioanalytical methodical approaches for the disposition monitoring of a new potential drug in organism using HPLC-PDA-MS-MS
dissertation thesis (DEFENDED)
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http://hdl.handle.net/20.500.11956/14216Identifiers
Study Information System: 53421
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- Kvalifikační práce [6393]
Author
Advisor
Referee
Chládek, Jaroslav
Wsól, Vladimír
Faculty / Institute
Faculty of Pharmacy in Hradec Králové
Discipline
Drug Control
Department
Department of Pharmaceutical Chemistry and Pharmaceutical Analysis
Date of defense
11. 2. 2008
Publisher
Univerzita Karlova, Farmaceutická fakulta v Hradci KrálovéLanguage
Czech
Grade
Pass
1. Summary The aim of this study consisted in the development and validation of a bioanalytical method for the identification and determination of dimefluron and its metabolites in biomatrices. For the purposes of this study, six expected potential dimefluron metabolites were prepared and identified by NMR and MS. Higher homologue of dimefluron (homodimefluron) was selected and synthesized as an internal standard. The chromatographic columns with various types of the stationary phases were tested. The best results were achieved using a pentafluorophenylpropylsilyl silica gel column rinsed with the mobile phase of acetonitrile- phosphate buffer pH = 3 in a gradient mode. After the validation of the bioanalytical method, this chromatographic system was applied to the disposition study of dimefluron in rats. After an intragastric administration of dimefluron to rats, samples of urine and faeces were collected each 24 hours. The elimination of dimefluron and its phase I and phase II metabolites in urine and faeces was studied. Maximum concentrations of dimefluron derivatives in the excrements were found in the time interval of 24 - 48 hours after the administration. 9-O-Desmethyldimefluron and 3-O-desmethyldimefluron were the principal metabolites found in the rat faeces, while the metabolic products of...