Pharmacokinetics and tissue distribution of five active ingredients of Eucommiae cortex in normal and ovariectomized mice by UHPLC-MS/MS

Abstract

1. Pinoresinol di-O-β-d-glucopyranoside (PDG), geniposide (GE), geniposidic acid (GA), aucubin (AN) and chlorogenic acid (CA) are the representative active ingredients in Eucommiae cortex (EC), which may be estrogenic.

2. The ultra high-performance liquid chromatography/tandem mass spectrometry (UHPLC-MS/MS) method for simultaneous determination of the five ingredients showed good linearity, low limits of quantification and high extraction recoveries, as well as acceptable precision, accuracy and stability in mice plasma and tissue samples (liver, spleen, kidney and uterus). It was successfully applied to the comparative study on pharmacokinetics and tissue distribution of PDG, GE, GA, AN and CA between normal and ovariectomized (OVX) mice.

3. The results indicated that except CA, the plasma and tissue concentrations of PDG, GE, GA in OVX mice were all greater than those in normal mice. AN could only be detected in the plasma and liver homogenate of normal mice, which was poorly absorbed in OVX mice and low in other measured tissues. PDG, GE and GA seem to be better absorbed in OVX mice than in normal mice proved by the remarkable increased value of AUC_0–∞ and C_max. It is beneficial that PDG, GE, GA have better plasma absorption and tissue distribution in pathological state.

• Bioanalysis
• Eucommiae cortex
• ovariectomized mice
• pharmacokinetics
• tissue distribution
• UHPLC-MS/MS

Acknowledgements

The authors acknowledge financial support from the Opening Project of Shanghai Key Laboratory of Complex Prescription (Shanghai University of Traditional Chinese Medicine, 13DZ2272300, ZK-1501).

Declaration of interest

This study was supported by the “Three-Year Action Plan Project” for the Development of TCM from Shanghai Health Bureau (ZYSNXD-GH-FFYJ, 2011-2013) and Postdoctoral fund Projects of China (3013M531203) and Shanghai (13R21415700). The authors report no conflicts of interest.