Pharmacokinetic and tissue distribution study of pectolinarigenin in rats using UPLC-MS/MS.
Abstract
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 (Tmax ≤ 0.222 h) and maintained at a low level with slow elimination (t1/2 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…
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