A simplified analytical method for a phenotyping cocktail of major CYP450 biotransformation routes

An efficient, fast and reliable analytical method was developed for the simultaneous evaluation of the activities of five major human drug metabolising cytochrome P450 (1A2, 2C9, 2C19, 2D6 and 3A4) with a cocktail approach including five probe substances, namely caffeine, flurbiprofen, omeprazole, d...

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Bibliographic Details
Published in:	Journal of pharmaceutical and biomedical analysis Vol. 35; no. 5; pp. 1203 - 1212
Main Authors:	Jerdi, Mallorie Clement, Daali, Youssef, Oestreicher, Mitsuko Kondo, Cherkaoui, Samir, Dayer, Pierre
Format:	Journal Article
Language:	English
Published:	Amsterdam Elsevier B.V 03-09-2004 Elsevier Science
Subjects:	Analysis Analytical, structural and metabolic biochemistry Biological and medical sciences Biotransformation Caffeine - blood Caffeine - metabolism Chromatography, High Pressure Liquid - methods Cocktail Cytochrome P-450 Enzyme System - genetics Cytochrome P-450 Enzyme System - metabolism Cytochrome P450 Dextromethorphan - blood Dextromethorphan - metabolism Flurbiprofen - blood Flurbiprofen - metabolism Fundamental and applied biological sciences. Psychology General pharmacology HPLC Humans Isoenzymes - metabolism Medical sciences Midazolam - blood Midazolam - metabolism Omeprazole - blood Omeprazole - metabolism Pharmacology. Drug treatments Phenotype Reproducibility of Results Sensitivity and Specificity Validation Validation Cocktail Cytochrome P450 HPLC Morphinan derivatives Prostaglandin-endoperoxide synthase Biological fluid H HPLC chromatography Opiates Dextromethorphan K Proton pump inhibitor Blood plasma Particle Prevention Biotransformation Arylpropionic acid derivatives Benzodiazepine derivatives Xanthine derivatives Caffeine Flurbiprofen Methanol Human Drug Fluorescence detector Enzyme Liquid liquid extraction Enzyme inhibitor Omeprazole Ultraviolet detector Benzimidazole derivatives exchanging ATPase Hydrolases Oxidoreductases Midazolam
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Summary:	An efficient, fast and reliable analytical method was developed for the simultaneous evaluation of the activities of five major human drug metabolising cytochrome P450 (1A2, 2C9, 2C19, 2D6 and 3A4) with a cocktail approach including five probe substances, namely caffeine, flurbiprofen, omeprazole, dextromethorphan and midazolam. All substances were administered simultaneously and a single plasma sample was obtained 2 h after the administration. Plasma samples were handled by liquid-liquid extraction and analysed by gradient high performance liquid chromatography (HPLC) coupled to UV and fluorescence detectors. The chromatographic separation was achieved using a Discovery semi-micro HS C18 HPLC column (5 μm particle size, 150 mm×2.1 mm i.d.) protected by a guard column (5 μm particle size, 20 mm×2.1 mm i.d.) The mobile phase was constituted of a methanol, acetonitrile and 20 mM ammonium acetate (pH 4.5) with 0.1% triethylamine mixture and was delivered at a flow rate of 0.3 mL min −1. All substances were separated simultaneously in a single run lasting less than 22 min. The HPLC method was formally validated and showed good performances in terms of linearity, sensitivity, precision and accuracy. Finally, the method was found suitable for the screening of these compounds in plasma samples.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0731-7085 1873-264X
DOI:	10.1016/j.jpba.2004.03.021