A simple method for the determination of Bosutinib in rat plasma by UPLC-MS/MS.

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 (2.1mm×50mm, 1.7μm) 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 0.1-500ng/mL (R(2)>0.9977) with a lower limit of quantification (0.1ng/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.