Determination of Poziotinib in Rat Plasma by UPLC-MS/MS and its Application to Pharmacokinetic Study

In this study, a robust analytical and sensitive method for the determination of poziotinib in rat plasma with enasidenib as internal standard (IS) was developed by UPLC-MS/MS. Chromatographic separation was performed on a CORTECS C18 column (2.1 x 50 mm, 1.6 mu m) with the mobile phase consisting of acetonitrile and water containing 0.1 % formic acid by gradient elution. Multiple reaction monitoring (MRM) mode with the positive electrospray ionization was quantified using target fragment ions m/z 492.06 -> 354.55 for poziotinib and m/z 474.57 -> 456.64 for enasidenib. Calibration curve was linear over the concentration range of 1-1000 ng/mL for poziotinib with a lower limit of quantification (LLOQ) of 1 ng/mL. RSD of inter-day and intra-day precision were both less than 14.61% with accuracy of the method at a range from 90.95 to 105.04%. Mean recovery of poziotinib and enasidenib in rat plasma was between 82.37% and 96.21%. The proposed method was successfully applied to a pharmacokinetic study of poziotinib after oral administration to rats.