LC-MS/MS Determination of Evodiamine in Plasma and Its Pharmacokinetics in Rats after Administration in the Form of Solid Lipid Nanoparticles

Background: A sensitive, reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed and applied to detect the evodiamine (EVO) in rat plasma after animals were given EVO directly. However there is almost no research on the detection of EVO after animals were given EVO-loaded solid lipid nanoparticles (EVO-SLN). Objective: In this study, a more sensitive and rapid modified LC-MS/MS method for the quantification of EVO in rat blood was developed and validated to evaluate the role of SLN in vivo. Methods: Plasma samples were taken from animals orally administered EVO-SLN or free EVO, proteins were extracted using diethyl ether containing the internal standards (IS) arbidol hydrochloride, and the mixture was fractionated by liquid chromatography. Quantitative detection of EVO was based on gradient elution in a mobile phase of acetonitrile-0.2% formic acid in water (70:30, v/v). Results: The calibration curve was linear (r(2)>0.999, n=9) over the concentration range from 0.1 to 250 ng/mL. Peaks in triple-quadrupole MS were detected for EVO at m/z 304.2 -> 134.1 and for IS at m/z 479.1 -> 343.0. Mean recovery of EVO was more than 93%. Intra and inter-day precision were within 2.7%. In pharmacokinetics studies, EVO-SLN exhibited much higher bioavailability and absorption than free EVO. Conclusion: The developed method in this work can provide a sensitive, effective and rapid process for the analysis of EVO in whole blood samples. The pharmacokinetics results suggest that the usefulness of SLN for improving oral bioavailability of poorly soluble drugs.