The <i>in vivo</i> pharmacokinetics, tissue distribution and excretion investigation of mesaconine in rats and its <i>in vitro</i> intestinal absorption study using UPLC-MS/MS

<p>1. Mesaconine, an ingredient from <i>Aconitum carmichaelii</i> Debx., has been proven to have cardiac effect. For further development and better pharmacological elucidation, the <i>in vivo</i> process and intestinal absorptive behavior of mesaconine should be investigated comprehensively.</p> <p>2. An ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the quantitation of mesaconine in rat plasma, tissue homogenates, urine and feces to investigate the <i>in vivo</i> pharmacokinetic profiles, tissue distribution and excretion. The intestinal absorptive behavior of mesaconine was investigated using <i>in vitro</i> everted rat gut sac model.</p> <p>3. Mesaconine was well distributed in tissues and a mass of unchanged form was detected in feces. It was difficultly absorbed into blood circulatory system after oral administration. The insufficient oral bioavailability of mesaconine may be mainly attributed to its low intestinal permeability due to a lack of lipophilicity. The absorption of mesaconine in rat’s intestine is a first-order process with the passive diffusion mechanism.</p>