Determination of 20(S)-protopanaxadiol ocotillol type epimers in rat plasma by liquid chromatography tandem mass spectrometry

To study stereoselectivity in the pharmacokinetics of each epimer, a rapid, specific and reliable liquid chromatography tandem mass spectrometry method has been established for simultaneous quantitation of both epimers in rat plasma. Plasma samples were pretreated by liquid-liquid extraction. Chromatographic separations were performed on a Shim-pack XR-ODS C18 column (50 mm × 2.1 mm, i.d., 2.2 μm) with an isocratic elution. Both epimers and the internal standard tanshinone II A were ionized with an ESI source operated in positive ion mode and measured by selective reactions monitoring mode. Calibration curve was linear over the concentration range of 1–1000 ng/mL with the lower limit of quantitation of 1 ng/mL for both epimers. Intra and inter-day precisions were less than 6.7% and 9.5%, and the accuracy was within ±5.8% for both epimers. The validated method has been successfully applied to a pharmacokinetic study of the two epimers in rats after oral administration.

► We synthesis the 20(S)-protopanaxadiol ocotillol type epimers. ► We developed a LC–MS/MS method to simultaneously quantitate of two epimers. ► The method was applied to study pharmacokinetics of two epimers. ► We found the stereoselectivity in pharmacokinetics of two epimers was different. ► The study could initially interpret pharmacological effect differences of two epimers.