Abstract

Background: 7, 8-dihydroxyflavone (7, 8-DHF) has been discovered to be a TrkB receptorspecific agonist and demonstrated remarkable therapeutic efficacy in vivo. These promising findings prompted the current pharmacokinetic study, in which we first established a practical LC-MS quantitative method for 7, 8-DHF then applied it in a pilot pharmacokinetic study in rats.

Methods: A simple HPLC-MS system was employed for the determination of 7, 8-DHF in rat plasma after the plasma samples were extracted with ethyl acetate by vortex-mixing. The method was thoroughly validated regarding accuracy, precision, sensitivity, linearity, selectivity, recovery, and stability.

Results: This method exhibited linearity within the concentration range of 9.024 (LLOQ) and 1128 ng/mL. The accuracy ranged from 87.9 to 105.6% of the actual values. The intra- and inter-day precisions ranged from 1.7 to 5.1% and from 2.2 to 4.4% (RSD, %). In the pharmacokinetic study, 7, 8-DHF was detectable in rat plasma for up to 24 h, with a terminal half-life of 22.8 h.

Conclusion: Overall, the results showed that this method was fully validated and successfully applied to a pilot pharmacokinetic study, which will facilitate the determination of the pharmacokinetic profile of 7, 8-DHF in future animal studies.

Keywords: 7, 8-dihydroxyflavone, HPLC-MS, neuroprotective agent, pharmacokinetics, determination, oral.

Graphical Abstract