High-throughput approaches to the quantitative analysis of ketoconazole, a potent inhibitor of cytochrome P450 3A4, in human plasma.

摘要: Ketoconazole, an imidazole-piperazine compound, is orally active antimycotic agent. In addition, ketoconazole a specific inhibitor of cytochrome P450 3A4. As about 60% oxidized drugs are biotransformed by this isoform, the potential effect concomitant administration on drug disposition may be interest during development. The present paper describes three different approaches (methods A, B, and C) to attain high-throughput sample preparation analysis in quantification human plasma. Method A consisted acetonitrile precipitation 96-well plate, transfer supernatant via Tomtec Quadra 96 Model 320, subsequent injection onto 50 x 4.6 mm (i.d.) Develosil Combi-RP-5 column (packed with C30 bonded silica particles). B identical method exception that Michrom Magic Bullet(trade mark) column, 2.0 --> 0.50 (i.d., tapered bore) x25 length, was used. Lastly, C, turbulent-flow chromatography (TurboFlow LC/APCI-MS/MS) module used for direct Sciex API 3000 methods while Micromass Quattro LC employed C. Based values obtained calibrator (standard) quality control samples, all protocols yielded satisfactory accuracy, precision, reduced manual time.