Using UPLC-MS/MS and LC-MS/MS to Investigate the Pharmacokinetics in SD Rat Plasma and Tissue Distribution in KM Mice...

Daphnoretin (DAP) has various pharmacological activities, but its in vivo disposition after nanomicellar formulation remains unclear. This study compared the pharmacokinetics and tissue distribution of free DAP and two polymeric nanomicellar formulations, PP-DAP and GA-DAP, following intravenous administration. Plasma DAP concentrations in rats were determined by UPLC-MS/MS, and DAP concentrations in mouse tissues were determined by LC-MS/MS. Compared with free DAP, PP-DAP and GA-DAP showed higher systemic exposure, longer apparent elimination half-lives, and lower apparent clearance. The AUC_0-∞ values of DAP, PP-DAP, and GA-DAP were 5474.14, 11,211.04, and 15,019.86 h · ng/mL, respectively, and the corresponding T_1/2 values were 6.84, 9.24, and 9.90 h. DAP was detected in the heart, liver, spleen, lung, and kidney, with the nanomicellar formulations showing altered tissue distribution and GA-DAP exhibiting relatively sustained hepatic distribution. These findings suggest that nanomicellar formulation alters the in vivo disposition of DAP. However, free and micelle-associated DAP were not separately quantified, precluding direct characterization of in vivo drug release, and the validation range of the tissue quantification method was limited. Further studies are warranted to evaluate the in vivo behavior and liver-directed delivery potential of GA-DAP.