Specific method for determination of OSI-774 and its metabolite OSI-420 in human plasma by using liquid chromatography-tandem mass spectrometry.
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.
Zhao
Ming
M
Division of Experimental Therapeutics, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, MD 21231-1000, USA.
He
Ping
P
Rudek
Michelle A
MA
Hidalgo
Manuel
M
Baker
Sharyn D
SD
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
C487471:OSI-420; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride