Validated UHPLC–MS/MS method for simultaneous determination of four triterpene saponins from Akebia trifoliata extract in rat plasma and its application to a pharmacokinetic study

Abstract

Saponin PH, akemisaponins E, saponin PJ 1 and scheffoleoside A, the main bioactive triterpene saponins of Chinese traditional medicine Akebia trifoliata, contribute to its diuretic pharmacological activity. Because of interactions of the multiple ingredients in vivo, pharmacokinetic studies of multiple triterpenes after administration of A. trifoliata extract are essential to clarify their pharmacological effects. The purpose of this study was to develop an efficient and sensitive UHPLC-MS/MS method for simultaneous determination of these four triterpene saponins in rat plasma.The biosamples were prepared by liquid-liquid extraction with n-butanol. The chromatographic separation was performed on a Phenomenex Luna ® C 18 (150 × 2 mm, 3 μm) with a mobile phase consisting of acetonitrile and water at a flow rate of 0.5 mL/min. The MS/MS system was operated in a negative multiple reaction monitoring mode, and the precursor-product ion transitions were optimized as m/z 941.6 → 471.1 for saponin PH, 941.7 → 471.2 for akemisaponins E, 1089.7 → 601.1 for saponin PJ 1 , 957.6 → 487.4 for scheffoleoside A and 799.5 → 637.3 for ginsenoside Rg 1 (Rg 1 , internal standard). Method validation parameters (calibration curve linearity, lower limit of detection, recovery, matrix effect, intra-and inter-day precision) were within the acceptable ranges. This is the first reported on the UHPLC-MS/MS detection of saponin PH, akemisaponins E, saponin PJ 1 and scheffoleoside A, and applied to a preclinical pharmacokinetic study after oral administration of A. trifoliata extract in rats. This study provides a basis for clinical application and further development of A. trifoliata extract.

Quantification of 10 bioactive components of Yazhangsan in rat plasma by LC–MS/MS and its application

“…The stabilities of these 10 analytes in rat plasma were determined by measuring the QC samples at three concentrations under different storage conditions (Chen et al, 2019). The freeze–thaw stability was assessed by analyzing QC samples over three freeze–thaw cycles.…”

A Systematic Study of Yiqi Qubai Standard Decoction for Treating Vitiligo Based on UPLC-Q-TOF/MS Combined with Chemometrics, Molecular Docking, and Cellular and Zebrafish Assays

“…P2 and P4 are the signature active ingredients of JQG and YZZ, respectively [34,35]. Due to low oral bioavailability and a short half-life, the components with high responses in vitro (C13, C24, C30, and C31) were not found as prototypes or metabolites in vivo [36][37][38]. By studying the metabolic pathways in detail, we found that the metabolites were mainly from glucuronidation, sulfation, hydroxylation, and demethylation reactions of the flavonoids in YQD.…”

Natural Triterpenoids Isolated from Akebia trifoliata Stem Explants Exert a Hypoglycemic Effect via α‐Glucosidase Inhibition and Glucose Uptake Stimulation in Insulin‐Resistant HepG2 Cells

“…The dried stems of A. trifoliata have also been used in traditional Chinese medicine for antineoplastic activity, activating blood circulation, facilitating diuresis, and suppressing urinary stones and oligogalactia (ChPC, 2015) in China for hundreds of years [20] . Recently, phytochemical investigations have been conducted on the stem and fruit sections of this plant, which contain a variety of bioactive constituents; triterpenoids, phenolics, flavonoids, and lignans have been identified, and some exhibit important bioactivity properties, including antioxidant, antimicrobial, antitumor, and antidiabetic activities [21–24] . However, previous studies mainly concentrated on the α‐glucosidase inhibitory activity of A. trifoliata and its chemical constituents, but the mechanism of action underlying these effects remains to be elucidated.…”