Comparative Pharmacokinetic Studies of Four Ginsenosides in Rat Plasma by UPLC-MS/MS after Oral Administration of Panax quinquefolius-Acorus gramineus and Panax quinquefolius Extracts.

Hailong Xie,Wenjun Zhang,Dongxue Wang,Xinjia Yan,Ying Zhao

doi:10.1155/2019/4972816

Abstract

Panax quinquefolius (PQ) and Acorus gramineus (AG) are drug target pairs in traditional Chinese medicine (TCM), which are used to treat age-related diseases. In the present study, we simultaneously determined the contents of four main bioactive ginsenosides (Rb1, Rb2, Rd, and Re) in rat plasma using an ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method. Plasma specimens were purified by using the solid-phase extraction procedure, and separation was performed on Waters ACQUITY UPLC BEH C18 (100 mm × 2.1 mm, 1.7 μm) in multiple reaction monitoring (MRM) mode and negative electrospray ionization (ESI) mode. The established UPLC-MS/MS method showed good linear correlation (r ≥ 0.9978), stability (−11.93 to 12.11%), precision (RSD < 14.63%), and recovery (76.43%–95.20%). The lower limit of quantification was 3.6 ng/mL for Rb1, 1.6 ng/mL for Rb2, 1.2 ng/mL for Rd, and 2.5 ng/mL for Re. This validated method was successfully employed to investigate the pharmacokinetics of the four ginsenosides in rat plasma after oral administration of PQ-AG and PQ extracts. The results revealed the pharmacokinetic profiles of PQ-AG drug pair and clarified that AG played a critical role in stimulating the absorption of active ginsenosides in PQ. Collectively, our findings provided valid and reliable evidence for the rational use of PQ-AG in clinical practice.

Highlights

In multiple diseases caused by complex pathogenic factors, the advantages of using a single herb are absent or show weaker meaning. e drug target pairs are the combination of two relatively fixed drugs based on the theory of traditional Chinese medicine (TCM), showing important clinical significance in various diseases [1,2,3,4]
Because only few reports have assessed the pharmacokinetic profiles and the compatibility mechanism of the drug pair, we developed an ultra-performance liquid chromatography coupled with a triple quadrupole electrospray tandem mass spectrometry (UPLC-MS/MS) method to compare the pharmacokinetic profiles of four major bioactive components of ginsenosides, Rb1, Rb2, Rd, and Re (Figure 1) in rat plasma after oral administration of Panax quinquefolius (PQ)-Acorus gramineus (AG) and single PQ extracts
We found that acetonitrile/H2O system offered the best performance among different mobile phases, including methanol/water, acetonitrile/water, and methanol/acetonitrile/

Summary

Introduction

In multiple diseases caused by complex pathogenic factors, the advantages of using a single herb are absent or show weaker meaning. e drug target pairs are the combination of two relatively fixed drugs based on the theory of traditional Chinese medicine (TCM), showing important clinical significance in various diseases [1,2,3,4]. E drug target pairs are the combination of two relatively fixed drugs based on the theory of traditional Chinese medicine (TCM), showing important clinical significance in various diseases [1,2,3,4]. Panax quinquefolius (PQ) is used to restore vital energy and treat diabetes [5] and tumor [6] as Qi-tonifying agents in TCM. As described in early publications and our previous studies, PQ-AG drug pair is popular due to its remarkable and reliable therapeutic actions, such as antioxidant, antiaging, and blood circulation promoting properties, especially in treating diabetes [13,14,15]. Some methods have been used for the determination of ginsenosides. An LC-MS/MS method has been established to determine the concentrations of ginsenosides in plasma and brain [16]. An LC-MS fingerprint and a chemometric approach, in combination with multivariate statistics, have been used to distinguish between P. quinquefolius samples derived from the United States and China [18]

Methods

Results

Conclusion