Evaluation of the Pharmacokinetics of the Simultaneous Quantification of Letrozole and Palbociclib in Rat Plasma by a Developed and Validated HPLC-PDA

Abstract

The US Food and Drug Administration (FDA) has affirmed the use of letrozole (LTZ) combined with palbociclib (PLB) to treat breast malignant tumor growth in postmenopausal women. A straightforward and extremely sensitive reversed-phase high-performance liquid chromatography method with photodiode array detection (RP-HPLC-PDA) was created and validated for the simultaneous determination of LTZ and PLB in rat plasma. The parameters used to give the best separation were a C18 column (150 mm × 4.6 mm, 3.5 μm) as the stationary phase with an isocratic mobile phase composed of methanol-30 mM ammonium acetate at a ratio of 60:40 (v/v), pH = 5.5, a flow rate of 0.8 mL/min, and detection wavelengths of 240 and 220 nm for LTZ and PLB, respectively. The developed method was assessed by the FDA rules over a range of 10-600 ng/mL for LTZ and PLB. The mean of %recovery of LTZ and PLB extracted from rat plasma by acetonitrile-based deproteinization was 91.06 ± 2.73 and 90.30 ± 1.95%, respectively, and the limits of detection were 5 ng/mL for LTZ and 7 ng/mL for PLB in rat plasma. The mean values of Tmax and Cmax were 6 ± 0.00 h and 266.96 ± 21.23 ng/mL for LTZ and 4 ± 0.00 h and 508.75 ± 61.56 ng/mL for PBL, respectively, after intraperitoneal administration of both drugs to rats. The developed HPLC-PDA method was demonstrated to be robust and was effectively applied to study the pharmacokinetics of LTZ and PLB in rat plasma.