Pharmacokinetic and bioavailability study of 5-hydroxy-4-methoxycanthin-6-one, a typical canthinone alkaloid, in rats by ultra-high performance liquid chromatography/electrospray ionization tandem mass spectrometry.

Hydroxy-4-methoxycanthin-6-one, a major canthinone alkaloid isolated from Picrasma quassioides, exhibited significant pharmacological activities. In the present study, a rapid and sensitive liquid chromatography tandem mass spectrometry method was established and validated for the determination of 5-Hydroxy-4-methoxycanthin-6-one in rat plasma. Small quantities (20 muL) of plasma sample was used for sample preparation. 5-Hydroxy-4-methoxycanthin-6-one and internal standard (caffeine, IS) were separated on a Waters ACQUITY(TM) HSS T3 (50 mm x 2.1 mm, 1.7 mum) column. The mobile phase was composed of 0.1% formic acid in water and acetonitrile. Precursor-to-product ion transitions were m/z 267.0-->168.2 and m/z 195.0-->138.1 for quantitative monitoring of 5-Hydroxy-4-methoxycanthin-6-one and IS, respectively. The assay was linear over the concentration range of 0.5-500 ng/mL (r > 0.99) with the LLOQ 0.5 ng/mL. Other parameters including intra- and inter-day precision and accuracy, carry-over, stability, extraction recovery, matrix effect and dilution effect were within the acceptable limits. The validated method was successfully applied to pharmacokinetic study in rats after intravenous (5 mg/kg) and oral (10, 25, 50 mg/kg) administration of 5-Hydroxy-4-methoxycanthin-6-one. The result suggested that 5-Hydroxy-4-methoxycanthin-6-one was quickly absorbed into blood and reached the highest concentration at approximately 33.0-42.0 min, with moderate elimination half-life (0.85-2.11 h) and low bioavailability (16.62-24.42 %) followed oral administration. The study provided valuable information which can be used as a reference for the study of other canthinone alkaloids.