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A sensitive and rapid ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was developed to determine ibrutinib in rat plasma u sing carbamazepine as the internal standard (IS).Sample preparation wasaccomplished thro ugh a protein precipitation procedure with acetonitrile.The analyte and IS were separated o n an Acquity UPLC BEH C18 column (2.1 mm × 50 mm, 1.7 μm) with the mobile phase of acetonitrile and 1% formic acid in water with gradientelution at a flow rate of 0.40 mL/min The detection was performed on a triplequadrupole tandem mass spectrometer equipped with electrospray ionization (ESI) by multiple reactions monitoring (MRM) of the transitions at m/z 441.3 → 84.1 foribrutinib and m/z 237.1 → 194.1 for IS.The linearity of this method was found to be within the concentration range of 0.1-100 ng/mL with a lower limit of quantification of 0.1 ng/mL.Only 4.0 min was needed for an analytical run.The method here in described was superior to previous methods and was successfully applied to the pharmacokinetic study of ibrutinib in rat after oral administration.