A pharmacokinetic study on punicalagin following oral and intravenous administration to the rat using UPLC-MS/MS

Punicalagin (PUN) is a high abundant ellagitannin and the principal bioactive component existing in Pomegranate (Punica granatum L.) peel, juice, and extract, yet its absorption, bioavailability and pharmacokinetic parameters have not been adequately investigated after oral administration in vivo model. Thus, this study developed a reproducible UPLC-MS/MS method (linear range: 0.125-70 μg/mL; LLOQ: 0.125 μg/mL) to characterize PUN pharmacokinetic profile in Sprague-Dawley rats. After intravenous (iv, 10 mg/kg) administration, PUN exhibited slow elimination (iv, t_1/2 = 6.45 ± 2.11 h) and plasma-restricted distribution (V_d = 0.94 ± 0.23 L/kg). By intragastric route (ig, 100-400 mg/kg), PUN showed dose-dependent absorption (T_max ≈ 2 h), critically low absolute bioavailability (3.22-5.38%) and extensive tissue distribution (V_d = 14.0-44.5 L/kg). The area under the plasma concentration-time curve from time zero to last sampling time (AUC_0-t) and AUC_0-∞ (from time zero to infinity) were 30.0-211.5, 32.0-213.8 μg*h/mL. The C_max of PUN in plasma samples was ranged from 1.91 to 34.8 μg/mL. The dose proportionality study demonstrated the C_max and AUC_0-t values were positively correlated with ig doses, with R² (95% CI) being 0.858 (0.770-0.959) for C_max and 0.904 (0.847-0.956). Overall, the comprehensively detailed pharmacokinetic parameters of pure PUN have been determined, providing valuable information for preclinical study.