| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1213138 | Journal of Chromatography B | 2012 | 5 Pages |
A quantitative bioanalytical liquid chromatography–tandem mass spectrometric (LC–MS/MS) assay for the ALK inhibitor crizotinib was developed and validated. Plasma samples were pre-treated using protein precipitation with acetonitrile containing crizotinib-13C2-2H5 as internal standard. The extract was directly injected into the chromatographic system after dilution with water. This system consisted of a sub-2 μm particle, trifunctional bonded octadecyl silica column with a gradient using 0.1% (v/v) of ammonium hydroxide in water and methanol. The eluate was transferred into the electrospray interface with positive ionization and the analyte was detected in the selected reaction monitoring mode of a triple quadrupole mass spectrometer. The assay was validated in a 10–10,000 ng/ml calibration range with r2 = 0.99980 ± 0.00014 for double logarithmic linear regression (n = 5). Within day precisions (n = 6) were 3.4–4.8%, between day (3 days; n = 18) precisions 3.6–4.9%. Accuracies were between 107% and 112% for the whole calibration range. The drug was sufficiently stable under all relevant analytical conditions. Oxidative metabolites of crizotinib were monitored semi-quantitatively. Finally, the assay was successfully used to assess drug pharmacokinetics in mice.
► The first validated bioanalytical assay for crizotinib has been reported. ► The assay has successfully been validated in the 10–10,000 ng/ml range. ► The drug is stable under all conditions relevant for the assay. ► Oxidative metabolites can simultaneously be monitored. ► First pharmacokinetics in male wild type FVB mice have reported.
