Pharmacokinetic and tissue distribution study of pectolinarigenin in rats using UPLC-MS/MS

Pectolinarigenin (PEC), a natural flavonoid isolated from Cirsium japonicum, exhibits promising therapeutic potential for multiple cancers. In present study, a simple and sensitive UPLC-MS/MS method was established for the quantification of PEC in rat plasma and tissues. The assay procedure involved a one-step protein precipitation with tadalafil as the internal standard, and separation on a Welch Xtimate UHPLC C₁₈ column by gradient elution of acetonitrile/aqueous formic acid (0.1 %, v/v) at a flow rate of 0.2 m L·min⁻¹. The detection was conducted using multiple-reaction monitoring via an electrospray ionization source in positive ionization mode. The established method was proved to be highly sensitive with a good linearity (R² > 0.99) in respective concentration range (0.1–100 ng·mL⁻¹ in plasma and 1–10,000 ng·mL⁻¹ in tissues) and acceptable extraction recovery (≥71.17 %), matrix effect and stability, which was applied to study the pharmacokinetics and tissue distribution of PEC after intravenous (100 μg·kg⁻¹) and oral administration (10, 20 and 40 mg·kg⁻¹). PEC was promptly absorbed (T_max ≤ 0.222 h) and maintained at a low level with slow elimination (t_{1/2 z} ≥ 14.47 h) in rats after oral administration, resulting in extremely low bioavailability (0.56–0.68 %). However, PEC is widely distributed in rat tissues with high exposure in GI tract, liver and kidney. The bioavailability and tissue affinity were firstly revealed, which would guide directions for further development of PEC as an anti-tumor drug candidate.