Identification and Pharmacokinetic Studies on Complanatuside and Its Major Metabolites in Rats by UHPLC-Q-TOF-MS/MS and LC-MS/MS

Abstract

The metabolic and pharmacokinetic studies on complanatuside, a quality marker of a Chinese materia medicatonic, Semen Astragali Complanati, were carried out. The UHPLC-Q-TOF/MS (ultra-high performance liquid chromatography coupled with electrospray ionization tandem quadrupole-time-of-flight mass spectrometry) method was applied to identify the metabolites of complanatuside in rat plasma, bile, stool, and urine after oral administration at the dosage of 72 mg/kg. Up to 34 metabolites (parent, 2 metabolites of the parent drug, and 31 metabolites of the degradation products) were observed, including processes of demethylation, hydroxylation, glucuronidation, sulfonation, and dehydration. The results indicated glucuronidation and sulfonation as major metabolic pathways of complanatuside in vivo. Meanwhile, a HPLC-MS method to quantify complanatuside and its two major metabolites—rhamnocitrin 3-O-β-glc and rhamnocitrin—in rat plasma for the pharmacokinetic analysis was developed and validated. The Tmax (time to reach the maximum drug concentration) of the above three compounds were 1 h, 3 h, and 5.3 h, respectively, while the Cmax (maximum plasma concentrations)were 119.15 ng/mL, 111.64 ng/mL, and 1122.18 ng/mL, and AUC(0-t) (area under the plasma concentration-time curve) was 143.52 µg/L·h, 381.73 µg/L·h, and 6540.14 µg/L·h, accordingly. The pharmacokinetic characteristics of complanatuside and its two metabolites suggested that complanatuside rapidly metabolized in vivo, while its metabolites—rhamnocitrin—was the main existent form in rat plasma after oral administration. The results of intracorporal processes, existing forms, and pharmacokinetic characteristics of complanatuside in rats supported its low bioavailability.

Comparison of the Phenolic Profiles of Soaked and Germinated Peanut Cultivars via UPLC-QTOF-MS

“…Peak 29 was tentatively identified as complanatuside with a molecular ion [M–H] − at 623.1616, and fragment ions at m / z 463.08559 [ 0,4 B -2H 2 O] − , m / z 337.09246 [M–ring B–2H 2 O] − , which further lost one molecule of water and gave m / z 315.05056. Other fragment ions, such as m / z 301.03066 [ 1,4 B–H 2 O–glucopyranosyl] − , and m / z 299.05594 [M–glucopyranosyl–glucopyranosyl] − , also further confirmed its potential structure [37]. Similar mass data about complanatuside was also reported in Lepidium draba L. [38].…”

Complanatuside alleviates inflammatory cell damage induced by pro-inflammatory cytokines in skin keratinocytes

“…Complanatuside is a flavonol glycoside isolated from Astragalus complanatus , which is commonly used in traditional Chinese medicine clinics. Studies have shown that flavonoids from Astragalus complanatus exert anti-inflammatory, anticancer, and immuno-modulating activities ( Ng et al, 2014 ; Li et al, 2018 ; Yao et al, 2018 ). However, the anti-inflammatory effect and the protective effect of complanatuside on skin keratinocytes have not been reported.…”

“…That is commonly used as a traditional Chinese medicine in clinics. Flavonoids from Astragalus complanatus have been reported to exert inhibitory effects on inflammation and cancer ( Ng et al, 2014 ; Yao et al, 2018 ). In this study, IL-6, TNF-α, and IFN-γ were used to simulate “cytokine storm” to induce inflammatory injury in HaCaT cells.…”

In silicoidentification of natural antiviral compounds as a potential inhibitor of chikungunya virus non-structural protein 3 macrodomain

“…Complanatuside has anti-inflammation, lipid-lowering and hepatoprotective properties. Complanatuside pharmacokinetic analysis has been developed and validated (Yao et al 2018). Eriocitrin flavanone has beneficial health effects and has antioxidant activity (Cesari et al 2020); as many of these compounds, low water solubility, stability and shelf life are major issues of eriocitrin.…”