Title:LC-MS/MS Determination of Evodiamine in Plasma and Its Pharmacokinetics in Rats after Administration in the Form of Solid Lipid Nanoparticles
VOLUME: 16 ISSUE: 3
Author(s):Yi Feng, Huanli Yin, Xue Zhao and Min Wu*
Affiliation:Department of Pharmacy, Chengdu Medical College, No.683, Xindu Avenue, Xindu District, Chengdu, Sichuan Province, Department of Pharmacy, Chengdu Medical College, No.683, Xindu Avenue, Xindu District, Chengdu, Sichuan Province, Department of Pharmacy, Chengdu Medical College, No.683, Xindu Avenue, Xindu District, Chengdu, Sichuan Province, Department of Pharmacy, Chengdu Medical College, No.683, Xindu Avenue, Xindu District, Chengdu, Sichuan Province
Keywords:Evodiamine, pharmacokinetics, plasma, solid lipid nanoparticles, LC/MS, validation.
Abstract:
Background: A sensitive, reliable liquid chromatography-tandem mass spectrometry (LCMS/
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 (r2>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.