Abstract
A rapid, sensitive and specific method was developed and validated using liquid chromatography-tandem mass spectrometry (LC/MS/MS) for determination of gefitinib in human plasma and mouse plasma and tissue. Sample preparation involved a single protein precipitation step by the addition of 0.1 mL of plasma or a 200 mg/mL tissue homogenate diluted 1/10 in human plasma with 0.3 mL acetonitrile. Separation of the compounds of interest, including the internal standard (dS)-gefitinib, was achieved on a Waters X-Terra™ C18 (50 mm × 2.1 mm i.d., 3.5 μm) analytical column using a mobile phase consisting of acetonitrile-water (70:30, v/v) containing 0.1% formic acid and isocratic flow at 0.15 mL/min for 3 min. The analytes were monitored by tandem mass spectrometry with electrospray positive ionization. Linear calibration curves were generated over the range of 1-1000 ng/mL for the human plasma samples and 5-1000 ng/mL for mouse plasma and tissue samples with values for the coefficient of determination of >0.99. The values for both within- and between-day precision and accuracy were well within the generally accepted criteria for analytical methods (<15%). This method was subsequently used to measure concentrations of gefitinib in mice following administration of a single dose of 150 mg/kg intraperitoneally and in cancer patients receiving an oral daily dose of 250 mg.
Original language | English (US) |
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Pages (from-to) | 73-80 |
Number of pages | 8 |
Journal | Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences |
Volume | 819 |
Issue number | 1 |
DOIs | |
State | Published - May 5 2005 |
Keywords
- Gefitinib
- LC/MS/MS
- Pharmacokinetics
- ZD1839
ASJC Scopus subject areas
- Analytical Chemistry
- Biochemistry
- Clinical Biochemistry
- Cell Biology