Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Ardjomand-Woelkart, K; Kollroser, M; Li, L; Derendorf, H; Butterweck, V; Bauer, R.
Development and validation of a LC-MS/MS method based on a new 96-well Hybrid-SPE™-precipitation technique for quantification of CYP450 substrates/metabolites in rat plasma.
Anal Bioanal Chem. 2011; 400(8):2371-2381
Doi: 10.1007/s00216-010-4618-3
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- Co-Autor*innen der Med Uni Graz
- Kollroser Manfred
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- Abstract:
- A rapid and selective high-throughput HESI-LC-MS/MS method for determining eight cytochrome P450 probe drugs in one-step extraction and single run was developed and validated. The four specific probe substrates midazolam, dextromethorphan, tolbutamide, theophylline and their metabolites 1-hydroxymidazolam, dextrorphan, hydroxyl(methyl)tolbutamide, 1,3-dimethyluric acid, together with the deuterated internal standards, were extracted from rat plasma using a novel 96-well Hybrid-SPE™-precipitation technique. The bioanalytical assay was based on reversed phase liquid chromatography coupled with tandem mass spectrometry in the positive ion mode using selected reaction monitoring for drug (-metabolite) quantification. All analytes were separated simultaneously in a single run that lasted less than 11 min. The intra- and inter-day precisions for all eight substrates/metabolites were 1.62-12.81% and 2.09-13.02%, respectively, and the relative errors (accuracy) for the eight compounds ranged from -9.62% to 7.48% and -13.84% to 8.82%. Hence, the present method provides a robust, fast and reproducible analytical tool for the evaluation of four major drug metabolising cytochrome P450 (3A4, 2C9, 1A2 and 2D6) activities with a cocktail approach in rats to clarify herb-drug interactions. The method can be used as a basic common validated high-throughput analytical assay for in vivo interaction studies.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Chemical Precipitation -
- Chromatography, High Pressure Liquid -
- Cytochrome P-450 Enzyme System - blood
- Male -
- Molecular Structure -
- Pharmaceutical Preparations - blood
- Rats -
- Rats, Sprague-Dawley -
- Solid Phase Extraction -
- Stereoisomerism -
- Substrate Specificity -
- Tandem Mass Spectrometry -
- Find related publications in this database (Keywords)
- Hybrid-SPE (TM) precipitation
- Validation
- Phospholipids
- CYP450