Specific method for determination of OSI-774 and its metabolite OSI-420 in human plasma by using liquid chromatography-tandem mass spectrometry

J Chromatogr B Analyt Technol Biomed Life Sci. 2003 Aug 15;793(2):413-20. doi: 10.1016/s1570-0232(03)00356-8.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Calibration
  • Chromatography, Liquid / methods*
  • Dose-Response Relationship, Drug
  • Erlotinib Hydrochloride
  • Humans
  • Mass Spectrometry / methods*
  • Quinazolines / blood*
  • Quinazolines / pharmacokinetics
  • Reproducibility of Results
  • Sensitivity and Specificity


  • OSI-420
  • Quinazolines
  • Erlotinib Hydrochloride