| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1212952 | Journal of Chromatography B | 2015 | 5 Pages |
•A method was fully validated to determine bosutinib in rat plasma.•This is the most sensitive analysis for bosutinib.•The plasma sample was prepared by a protein precipitation.•Bosutinib was analyzed in rat plasma up to 48 h after administration.
In this work, a simple, sensitive and fast ultra performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the quantitative determination of bosutinib in rat plasma. Plasma samples were processed with a protein precipitation. The separation was achieved by an Acquity UPLC BEH C18 column (2.1 mm × 50 mm, 1.7 μm) column with a gradient mobile phase consisting of 0.1% formic acid in water and acetonitrile. Detection was carried out using positive-ion electrospray tandem mass spectrometry via multiple reaction monitoring (MRM). The validated method had an excellent linearity in the range of 0.1–500 ng/mL (R2 > 0.9977) with a lower limit of quantification (0.1 ng/mL). The extraction recovery was in the range of 75.6–85.6% for bosutinib and 81.2% for pirfenidone (internal standard, IS). The intra- and inter-day precision was below 9.7% and accuracy was from −8.1% to 8.8%. No notable matrix effect and astaticism was observed for bosutinib. The method has been successfully applied to a pharmacokinetic study of bosutinib in rats for the first time, which provides the basis for the further development and application of bosutinib.
