Gemfibrozil and its oxidative metabolites: quantification of aglycones, acyl glucuronides, and covalent adducts in samples from preclinical and clinical kinetic studies
| Autor: | Ann-Katrin Gräfe, Gül Baktir, Andreas Hermening, Hildegard Spahn-Langguth, Ernst Mutschler |
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| Rok vydání: | 2000 |
| Předmět: |
Detection limit
Chromatography Chemistry Reproducibility of Results Hyperlipidemias General Chemistry Reference Standards Alkaline hydrolysis (body disposal) Sensitivity and Specificity Rats Adduct Glucuronides Spectrometry Fluorescence Pharmacokinetics Covalent bond medicine Animals Humans Liberation Gemfibrozil Selectivity Chromatography High Pressure Liquid Hypolipidemic Agents medicine.drug |
| Zdroj: | Journal of Chromatography B: Biomedical Sciences and Applications. 741:129-144 |
| ISSN: | 0378-4347 |
| DOI: | 10.1016/s0378-4347(00)00041-4 |
| Popis: | A gradient reversed-phase HPLC analysis for the direct measurement of gemfibrozil (GEM) and four oxidative metabolites in plasma and urine of humans and in tissue homogenates of rats was developed. The corresponding acyl glucuronides and the covalently bound protein adducts (in protein precipitates) were determined after liberation from the respective conjugates via alkaline hydrolysis. The limits of detection for the covalent adducts in human plasma are: 10 ng ml(-1) (GEM), 20 ng ml(-1) (M1), 0.5 ng ml(-1) (M2, M4), and 5 ng ml(-1) (M3). The method was validated with respect to selectivity, recovery, linearity, precision, and accuracy. It has been applied to the analysis of preclinical and clinical studies. Pharmacokinetic profiles of gemfibrozil, its metabolites, and covalent adducts in human plasma and rat tissue homogenates are given. |
| Databáze: | OpenAIRE |
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