期刊
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
卷 400, 期 8, 页码 2371-2381出版社
SPRINGER HEIDELBERG
DOI: 10.1007/s00216-010-4618-3
关键词
Hybrid-SPE (TM) precipitation; Validation; Phospholipids; CYP450
资金
- The Austrian Science Fund (FWF) [J2754-B05]
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 (TM)-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.
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