Liquid chromatography-tandem mass spectrometry assay for the quantitation of plagiochin E and its main metabolite plagiochin E glucuronides in rat plasma

Plagiochin E, a macrocyclic bisbibenzyl isolated from liverwort Marchantia polymorpha, was found to have antifungal activity. To evaluate the pharmacokinetics of plagiochin E in rats, a sensitive and specific liquid chromatography/tandem mass spectrometric (LC-MS/MS) method was developed and validated for the quantitation of plagiochin E and its total conjugated metabolites in rat plasma. For detection, a Sciex API 4000 LC-MS/MS with a TurbolonSpray ionization (ESI) inlet in the negative ion-multiple reaction monitoring (MRM) mode was used. The plasma samples were pretreated by a simple liquid-liquid extraction with ethyl acetate. The concentration of plagiochin E parent form was determined directly and the concentration of plagiochin E conjugated metabolites was assayed in the form of plagiochin E after treatment with P-glucuronidase/sulfatase. The statistical evaluation for this method reveals excellent linearity, accuracy and precision for the range of concentrations 0.5-1000.0ng/mL. The method had a lower limit of quantification (LLOQ) of 0.5 ng/mL for plagiochin E in 50 mu L of plasma. The method was successfully applied to the characterization of the pharmacokinetic profile of plagiochin E in rats after an oral and an intravenous administration. (c) 2008 Elsevier B.V. All rights reserved.