Simultaneous determination of imperatorin and its metabolites in vitro and in vivo by a GC‐MS method: application to a bioavailability and protein binding ability study in rat plasma

Abstract

In this study, a simple and sensitive gas chromatography-mass spectrometry method was developed for the study of bioavailability and protein binding and the metabolism of imperatorin in rat. The results showed that the pharmacokinetics of imperatorin after intravenous and oral administration in rats exhibited linear characteristics. The absolute bioavailability of imperatorin was calculated as ~3.85, ~33.51 and ~34.76% for 6.25, 12.5 and 25 mg/kg, respectively. The low bioavailability of imperatorin may be attributed to the poor absorption or extensive metabolism. The phase I metabolites of imperatorin formed in vitro by rat liver microsomes were studied, and two metabolites were isolated and identified as xanthotoxol and heraclenin. Following oral administration of imperatorin, one metabolite (heraclenin) was detected in rat plasma, and two potential metabolites (xanthotoxol and heraclenin) were detected in rat urine. However, none of potential metabolites was detected in rat feces and bile. The results showed that the metabolites of imperatorin were excreted by kidney, and heraclenin was associated with an active component. Demethylation and oxygenization were the main metabolic pathways. In vitro plasma protein binding of imperatorin was 90.1 and 92.6% for the spiked rat plasma concentrations of 1.0 and 50.0 µg/mL, respectively, indicating that imperatorin showed slow distribution into the intra- and extracellular space.

Increased skin permeation efficiency of imperatorin via charged ultradeformable lipid vesicles for transdermal delivery

“…31 Considering the variety of pharmacological properties displayed by IMP, it is clear that the compound has the potential for development as a pharmaceutical formulation for subsequent clinical assessment. 32 Because of the low bioavailability of IMP, which may be attributed to its poor absorption or extensive metabolism, 33 topical application of IMP would be of great interest for its future use in clinical treatments. However, the high nonpolarity of IMP becomes an obstruction for delivering through the stratum corneum and viable epidermis, which greatly limits the percutaneous penetration of IMP.…”

A novel GC–MS method for determination of chrysophanol in rat plasma and tissues: Application to the pharmacokinetics, tissue distribution and plasma protein binding studies

“…The fraction of unbound drug was determined by the following equation: fu = Cu/Ct. Where fu is the fraction of unbound drug in plasma and Cu and Ct are the unbound and total concentrations of the drug in plasma, respectively [14,16].…”

“…It has been demonstrated that the PPB rate may affect the metabolic rates in the liver, the excretory rate from the kidney and the steady-state volume of distribution [16]. To date, equilibrium dialysis, microdialysis and ultrafiltration have become commonly available methods for measuring PPB [17,18].…”

Effects of drying methods on contents of bioactive compounds and antioxidant activities of Angelica dahurica

“…Xanthotoxin and bergapten result from complex furanocoumarin degradation during metabolisation, and imperatorin is demethylated to xanthotoxin [40]. As a result, xanthotoxin and bergapten content was increased with in-the-shade and 40°C drying.…”