Short communicationDetermination of oleanolic acid in human plasma and study of its pharmacokinetics in Chinese healthy male volunteers by HPLC tandem mass spectrometry
Introduction
Oleanolic acid [a, (3β)-3-hydroxyolean-12-en-28-oic acid (Fig. 1)] is one of the best known bioactive pentacyclic triterpenoids, that exists widely in medicinal herbs and plants, in the form of free acid or aglycones for triterpenoid saponins [1]. The traditional uses of plants containing oleanolic acid in folk medicines are multiple, in terms of anti-inflammatory [2], [3], hepato-protection, analgesia, cardiotonic, glucose-lowering [4], tonic effects and enhancement of the body defense systems, etc. It is now marketed in China as an oral drug for human liver disorders.
Approaches for measuring of oleanolic acid in rabbit plasma has been described by using UV–vis spectrophotometry [5]. But the reported method is not suitable for the pharmacokinetics study of oleanolic acid in human. There is not any reported pharmacokinetics data of oleanolic acid in human up until now. Therefore, a sensitive HPLC–ESI–MS–MS method was established for the determination of oleanolic acid in human plasma and the study of its pharmacokinetics.
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Materials
The reference substances of oleanolic acid and glycyrrhetinic acid were purchased from the National Institute for the Control of Pharmaceutical and Biological Products, Tiantanxili No. 2, Beijing, China. All chemicals and reagents used were of HPLC grade or analytical grade from the Nanjing Chemical Reagent Company, Yanyao Rd., Nanjing, China. The water was prepared with double distillation.
The oleanolic acid capsules (lot no: 20030301) were supplied by Zhuhai Rundu Pharmaceutical Co.,
Recovery, linearity, precision and accuracy
The Zorbax-Extend ODS analytical column and the mobile phase used for the determination gave a well-defined separation between the drug, internal standard and endogenous components. Typical chromatograms were shown in Fig. 3 with the retention time for glycyrrhetinic acid and oleanolic acid was about 3.0 and 6.3 min, respectively.
The absolute recoveries of both oleanolic acid and glycyrrhetinic acid from the plasma were more than 88% and less than 100%, indicating that most of oleanolic acid in
Conclusions
In summary, a novel sensitive HPLC–ESI–MS–MS method for the determination of oleanolic acid in human plasma has been developed and validated over the concentration range from 0.02 to 30.0 ng/ml. The method has been successfully used for the pharmacokinetics study of oleanolic acid in Chinese healthy male volunteers.
Acknowledgement
The authors would like to thank Dr. Dave G. Watson, Department of Pharmaceutical Sciences, University of Strathclyde, Glasgow G4 0NR, UK for his many helpful contributions during the course of the study and the writing of this manuscript.
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