title: Simultaneous determination of erlotinib and its isomeric major metabolites in human plasma using isocratic liquid chromatography-tandem mass spectrometry and its clinical application.
abstract: This study developed a method for the simultaneous determination of erlotinib and its isomeric major metabolites, OSI-413 and OSI-420, in human plasma using an isocratic liquid chromatography-tandem mass spectrometry. Plasma specimens deproteinized with acetonitrile were separated using a 3-µm particle size octadecylsilyl column. The m/z values of the precursor and product ions for the analytes were as follows: erlotinib, 394.2/278.2; and OSI-413 and OSI-420, 380.2/278.2. The total run time was 21 min and no peaks interfering with the analytes and internal standard (d6 -erlotinib) in human plasma were observed. The calibration curves of erlotinib, OSI-413 and OSI-420 were linear over the concentration ranges of 10-3000, 2-500 and 2-100 ng/mL, respectively. The pretreatment recovery ratios were >86.1%. The intra- and inter-assay precisions and accuracies were <12.7 and 89.0-108.9% for all analytes. This validated method was applied to the determination of plasma samples in lung cancer patients receiving 150 mg of oral erlotinib. The plasma concentration ranges of erlotinib, OSI-413 and OSI-420 were 373-2354, 15.7-379 and 2.5-43.6 ng/mL, respectively. In conclusion, the present method can be helpful for evaluating the plasma exposures of erlotinib and its major isomeric metabolites in clinical settings.
authors.affiliation: Department of Hospital Pharmacy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka, 431-3192, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Ishida
authors.forename: Takafumi
authors.initials: T
authors.lastname: Naito
authors.forename: Junichi
authors.initials: J
authors.lastname: Kawakami
mesh_terms: D000970:Antineoplastic Agents / Q000097:blood* / Q000737:chemistry / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood* / Q000188:drug therapy; D002853:Chromatography, Liquid / Q000379:methods*; D000069347:Erlotinib Hydrochloride / Q000097:blood* / Q000737:chemistry / Q000627:therapeutic use; D006801:Humans; D007536:Isomerism; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000970:Antineoplastic Agents; D000069347:Erlotinib Hydrochloride
keywords: LC-MS/MS; erlotinib; human plasma; isomeric metabolites; pharmacokinetics