Pharmacokinetics, tissue distribution and excretion study of dl-praeruptorin A of Peucedanum praeruptorum in rats by liquid chromatography tandem mass spectrometry

dl-Praeruptorin A (Pd-la), isolated from Chinese traditional herbal medicine Peucedanum praeruptorum Dunn, has been proved to be a novel Ca(2+)-influx blocker and K(+)-channel opener, and displayed bright prospects in prevention and therapy of cardiac diseases. The aim of this study was to investigate the pharmacokinetics, tissue distribution and excretion of Pd-la in rats following a single intravenous (i.v.) administration. The levels of Pd-la in plasma, tissues, bile, urine and feces were measured by a rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The results showed that Pd-la was rapidly distributed and then eliminated from rat plasma and manifested linear dynamics in dose range of 5-20 mg/kg. The mean elimination half-life (t(1/2)) of Pd-la for 5, 10 and 20 mg/kg dose were 57.46, 60.87 and 59.01 min, respectively. The major distribution tissues of Pd-la in rats were spleen, heart and lung, and low polarity enabled Pd-la to cross the blood-brain barrier. There was no long-term accumulation of Pd-la in rat tissues. Total recoveries of Pd-la within 24 h were low (0.097% in bile, 0.120% in urine and 0.009% in feces), which might be resulted from liver first pass effect. (C) 2010 Elsevier GmbH. All rights reserved.