An assessment of the impact of green tea extract on palbociclib pharmacokinetics using a validated UHPLC‐QTOF‐MS method

Autor: Patheparapu Chandrakala, David Paul, N. Satheeshkumar, Shruthi Surendran
Rok vydání: 2018
Předmět:
Zdroj: Biomedical Chromatography. :e4469
ISSN: 1099-0801
0269-3879
DOI: 10.1002/bmc.4469
Popis: Green tea extracts (GTE) has been reported to be a kinase inhibitor and modulator for various drug metabolizing enzymes. It may give synergetic antioncogenic effect, but with a possibility of pharmacokinetic interactions with various co-administered anticancer agents like palbociclib (PAL), a selective inhibitor of CDK-4/6 primarily metabolized by CYP3A enzyme. To explore the impact of GTE on PAL pharmacokinetics in Sprague-Dawley rats, a rapid and sensitive UHPLC-QTOF-MS method was established. Chromatographic separation was carried out on an Acquity UPLC BEH C18 (100 × 2.1 mm, 1.7 μm) column using a gradient mobile phase system consisting of 0.1% formic acid and acetonitrile. Sample preparation was based on a simple protein precipitation method. Estimation of target ions [M + H]+ at m/z 448.2455 for PAL and m/z 441.2044 for ibrutinib (IS) was performed in selective ion mode ESI-HRMS. Good sensitivity (1.0 ng/mL) and linearity over a wide concentration range of 1-2000 ng/mL was exhibited by the method. The results indicated that the administration of GTE resulted in decreased oral bioavailability of PAL in both short- and long-term conditions. However, when both conditions were compared, the variation was less for the peak concentration and area under the concentration-time curve level of PAL.
Databáze: OpenAIRE