Abstract
A sensitive and selective UHPLC-MS/MS method was developed and validated to simultaneously determine of palbociclib (PLB), letrozole (LTZ) and its metabolite carbinol (CBL) in rat plasma. After sample pre-treatment by acetonitrile-protein precipitation, the chromatographies resolution was performed using a reversed phase Acquity (R) UPLC BEH C18 column (1.7 mu m particle size, 50 mm x 2.1 mm ID) in isocratic mobile phase consisted of a mixture of methanol and water containing 0.1% acetic acid (55:45, v/v) at pH 4.5. The flow rate and run time were 300 mL/min and 2.5 min, respectively. The target drugs were detected in multiple reaction monitoring (MRM) mode using tandem mass spectrometer coupled to a positive ESI interface to monitor the precursor-to-product ion transitions. Method validation was assessed as per the FDA guidelines for determination of PLB, LTZ and CBL within the concentration ranges 0.5-600 ng/mL for PLB and LTZ and 0.2-200 ng/mL for CBL (r(2) >= 0.997). The rest of validation parameters were within the accepted limits. The validated method was applied to PK study of these drugs in rats, and succeeded to determine the values of the PK parameters of PLB and LTZ. (C) 2019 Production and hosting by Elsevier B.V. on behalf of King Saud University.