Determination of Flumatininb in Rat Plasma by UPLC-MS/MS: Application to a Pharmacokinetic Study

An accurate and validated liquid chromatography method with triple quadrupole mass spectrometer has been developed for detecting flumatinib in rat plasma. A reversed-phase CORTECS BEH C18 column kept at 40 degrees C was used. Acetonitrile and water (0.01% formic acid) was used as mobile phase, pumped at a flow rate of 0.4 mL/min. Samples were prepared by precipitating protein with acetonitrile. The analytes were detected using a Waters triple quadrupole mass spectrometer with positive electrospray ionization in multiple reaction monitoring (MRM) mode for target fragment ions m/z 563.22 -> 58.22 for flumatinib and m/z 557.3 -> 112.15 for neratinib(IS). Good linearity for flumatinib was gained with concentration ranges of 1-1000 ng/mL and 0.1 ng/mL for the lower limit of quantification in this assay. Mean recovery of flumatinib from plasma was better than 86.6%. This validated method applied to a pharmacokinetic study of flumatinib after oral (10 mg/kg) or intravenous (5 mg/kg) administration in rats was performed successfully.