PMID: 11334347May 4, 2001Paper

High-throughput cytochrome P450 (CYP) inhibition screening via cassette probe-dosing strategy. II. Validation of a direct injection/on-line guard cartridge extraction-tandem mass spectrometry method for CYP2D6 inhibition assessment

Journal of Chromatography. B, Biomedical Sciences and Applications
H Z BuP Teitelbaum

Abstract

A highly efficient direct injection/on-line guard cartridge extraction-tandem mass spectrometry (DI/GCE-MS-MS) method has been validated for high-throughput evaluation of cytochrome P450 (CYP) 2D6 inhibition potential using human hepatic microsomes and 96-well microtiter plates. Microsomal incubations were terminated with formic acid, centrifuged, and the resulting supernatants were injected for DI/GCE-MS-MS analysis. Due to the novel use of an extremely short C18 guard cartridge, this method exhibits several advantages, such as no sample preparation, excellent on-line extraction, short run time (2.5 min), and minimized source contamination and performance deterioration. The DI/GCE-MS-MS method demonstrates acceptable accuracy and precision for the quantification of dextrorphan, a marker metabolite of dextromethorphan mediated by CYP2D6, in microsomal incubations. The CYP2D6 inhibition assay has been validated using quinidine as a known selective inhibitor of the isoform. The IC50 value (0.20 microM) measured by the new method is in good agreement with the literature value (0.22 microM).

References

Aug 1, 1993·Pharmacogenetics·E Jacqz-AigrainT Cresteil
Mar 16, 2000·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·H YinD Moore

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Citations

Jul 27, 2001·Journal of Mass Spectrometry : JMS
Jan 26, 2007·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Jeroen KoolNico P E Vermeulen

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