Simultaneous quantification of two canthinone alkaloids of Picrasma quassioides in rat plasma by liquid chromatography-tandem mass spectrometry and its application to a rat pharmacokinetic study.

Abstract

Picrasma quassioides (D. Don) Benn. is used in traditional Chinese medicine for the treatment of inflammation. Characteristic components of the medicinal extract are canthinone alkaloids. In this study, a sensitive and rapid liquid chromatography with tandem mass spectrometry method has been developed for simultaneous quantification of two major canthinone alkaloids, 5-hydroxy-4-methoxycanthin-6-one and 4,5-dimethoxycanthin-6-one, in rat plasma after oral administration of P. quassioides extract (200 mg/kg). The chromatographic separation was performed on a C18 column using acetonitrile-aqueous 0.1% formic acid (90:10, v/v) as the mobile phase. Plasma samples were prepared for analysis using a simple liquid-liquid extraction with ethyl acetate. Analytes were detected using tandem mass spectrometry in positive multiple reaction monitoring mode. Method validation revealed excellent linearity over the range 1.25-900 ng/mL for 5-hydroxy-4-methoxycanthin-6-one and 0.5-800 ng/mL for 4,5-dimethoxycanthin-6-one with satisfactory intra- and inter-day precision, accuracy and recovery. Samples were stable under the conditions tested. The pharmacokinetic profiles of the analytes in rats showed that both canthinones were rapidly absorbed and that 4,5-dimethoxycanthin-6-one was eliminated faster than 5-hydroxy-4-methoxycanthin-6-one.