title: Specific method for determination of OSI-774 and its metabolite OSI-420 in human plasma by using liquid chromatography-tandem mass spectrometry.
abstract: A new simple and specific method was developed and validated for the quantitative determination of OSI-774 (Tarceva, Erlotinib) and its metabolite, OSI-420, in human plasma. Sample pretreatment involved a single protein precipitation step with acetonitrile. The analytes were separated on Waters X-Terra C(18) (50 x 2.1 mm I.D., 3.5 microm) analytical column and eluted with acetonitrile-water mobile (70:30, v/v) containing 0.1% formic acid. The analytes of interest were monitored by tandem mass spectrometry with electrospray positive ionization. The overall extraction efficiency was greater than 88% for OSI-774 and 62% for OSI-420, with values for within-day and between-day precision and accuracy of <15%. Compared to previous assays, this method is simple, specific, and reproducible and will be used to characterize the plasma pharmacokinetics of OSI-774 at doses of 50 to 150 mg to optimize treatment with this agent.
authors.affiliation: Division of Experimental Therapeutics, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, MD 21231-1000, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhao
authors.forename: Ping
authors.initials: P
authors.lastname: He
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Rudek
authors.forename: Manuel
authors.initials: M
authors.lastname: Hidalgo
authors.forename: Sharyn D
authors.initials: SD
authors.lastname: Baker
mesh_terms: D002138:Calibration; D002853:Chromatography, Liquid / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D000069347:Erlotinib Hydrochloride; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D011799:Quinazolines / Q000097:blood* / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: C487471:OSI-420; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride