Detection of 13 Ginsenosides (Rb1, Rb2, Rc, Rd, Re, Rf, Rg1, Rg3, Rh2, F1, Compound K, 20(S)-Protopanaxadiol, and 20(S)-Protopanaxatriol) in Human Plasma and Application of the Analytical Method to Human Pharmacokinetic Studies Following Two Week-Repeated Administration of Red Ginseng Extract.

Sojeong Jin,Woo Youl Kang,Young-Ran Yoon,Min-Koo Choi,Ji-Hyeon Jeon,Im-Sook Song,Sook Jin Seong,Sowon Lee

doi:10.3390/molecules24142618

Abstract

We aimed to develop a sensitive method for detecting 13 ginsenosides using liquid chromatography–tandem mass spectrometry and to apply this method to pharmacokinetic studies in human following repeated oral administration of red ginseng extract. The chromatograms of Rb1, Rb2, Rc, Rd, Re, Rf, Rg1, Rg3, Rh2, F1, compound K (CK), protopanaxadiol (PPD), and protopanaxatriol (PPT) in human plasma were well separated. The calibration curve range for 13 ginsenosides was 0.5–200 ng/mL and the lower limit of quantitation was 0.5 ng/mL for all ginsenosides. The inter- and intra-day accuracy, precision, and stability were less than 15%. Among the 13 ginsenosides tested, nine ginsenosides (Rb1, Rb2, Rc, Rd, Rg3, CK, Rh2, PPD, and PPT) were detected in the human plasma samples. The plasma concentrations of Rb1, Rb2, Rc, Rd, and Rg3 were correlated with the content in red ginseng extract; however, CK, Rh2, PPD, and PPT were detected although they are not present in red ginseng extract, suggesting the formation of these ginsenosides through the human metabolism. In conclusion, our analytical method could be effectively used to evaluate pharmacokinetic properties of ginsenosides, which would be useful for establishing the pharmacokinetic–pharmacodymic relationship of ginsenosides as well as ginsenoside metabolism in humans.

Highlights

Ginsenosides are classified into two types according to their hydroxylation position on the core triterpene saponin structure: 20(S)-protopanaxadiol (PPD) and 20(S)-protopanaxatriol (PPT) [1]
In rats, following single or repeated oral administration of high doses of ginseng extract (2–8 g/kg), various ginsenosides such as Ra3, Rb1, Rd, compound K (CK), Re, and Rg1 could be detected in the plasma of rats by LC-MS/MS with calibration curves ranging from 1.37 or 12.3 ng/mL to 3000 ng/mL [18]. These results suggest that sensitive analytical methods could be useful for the detection of various ginsenosides in human plasma
The results showed that inter-day and intra-day precision (CV in Table 3) for the 13 ginsenosides was below 13.0%, and the inter-day and intra-day accuracy (RE in Table 3) for the 13 ginsenosides was below 15.0% (Table 3)

Summary

Introduction

Ginsenosides are classified into two types according to their hydroxylation position on the core triterpene saponin structure: 20(S)-protopanaxadiol (PPD) and 20(S)-protopanaxatriol (PPT) [1]. These ginsenosides are considered to be the major active pharmacological constituents of ginseng [2,3]. Molecules 2019, 24, 2618 ginsenosides vary depending on the preparation method of ginseng product such as steaming times, temperature, and the extraction method [9,10]. Ginsenosides Rg1 and Re decreased, but ginsenosides Rb1, Rb2, Rc, Rd, and Rg3 increased after several hours of steaming and extraction. The oral bioavailability of Rb1 and Rh2 is around

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Conclusion