title: Determination of an in vivo metabolite of a human immunodeficiency virus protease-inhibitor in human plasma by high-performance liquid chromatography with tandem mass spectrometry.
abstract: A method for the determination of a metabolic of the human immunodeficiency virus protease inhibitor indinavir, in human plasma is described. Isolation of the analyte and the internal standard from plasma was achieved via liquid-liquid extraction with a mixture of isopropanol-chloroform (5:95, v/v). The analytes were chromatographed under reversed-phase conditions on a Waters Symmetry C, column. A Sciex API III+ tandem mass spectrometer equipped with a heated nebulizer was used as a detector and was operated in the positive ion mode. Multiple reaction monitoring using the precursor-->production combinations of m/z, 523.4-->273.4 and 512.4-->345.2 was used to quantify analyte and internal standard, respectively. The method was validated in the concentration range of 5-500 ng/ml plasma with adequate assay precision and accuracy. The assay was used to analyze samples collected during drug interaction studies of indinavir.
authors.affiliation: Merck Research Laboratories, Department of Drug Metabolism, PA 19486, USA.
authors.forename: E
authors.initials: E
authors.lastname: Woolf
authors.forename: H M
authors.initials: HM
authors.lastname: Haddix
authors.forename: B
authors.initials: B
authors.lastname: Matuszewski
mesh_terms: D000935:Antifungal Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D002940:Circadian Rhythm; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D019469:Indinavir / Q000008:administration & dosage / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D007654:Ketoconazole / Q000008:administration & dosage / Q000493:pharmacokinetics; D016014:Linear Models; D013058:Mass Spectrometry / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D000935:Antifungal Agents; D017320:HIV Protease Inhibitors; D019469:Indinavir; D007654:Ketoconazole