Metabolite identification and pharmacokinetic study of platycodi radix (Jiegeng) in vivo

Abstract

Platycodi radix (Jiegeng) is commonly used as a channel ushering drug for assistance in treating respiratory diseases, because of the activities of saponins that are called platycosides. In this study, using ultra high pressure liquid chromatography with quadrupole time of flight mass spectrometry (UPLC-Q/TOF-MS) and a strategy based on fragmentation behaviors, a total of thirteen platycosides were identified in the total saponins, and seven of these were found in rat plasma following a single oral dose of total saponins. The secondary platycosides were proved to be the main absorbed saponins in vivo. The major absorbed platycosides, 3-O-β-D-glucopyranosylplatyconic acid (GPA) and 3-O-β-D-glucopyranosylplatycodigenin (GP), were isolated from total saponins and the pharmacokinetics were evaluated in mice by liquid chromatography with triple quadrupole mass spectrometry (LC-QQQ). The results of the pharmacokinetic analysis indicated that GPA and GP were quickly absorbed with short T_max (<45 min). C_max (μg L⁻¹), AUC_0–t (μg h L⁻¹) and MRT_0–t (h) of GPA were 1147.75 ± 307.23, 2119.16 ± 530.84 and 4.10 ± 0.33 at a dose of 105 mg kg⁻¹, and 3673.10 ± 1250.44, 8734.07 ± 2362.48 and 3.95 ± 0.82 at a dose of 350 mg kg⁻¹. The above pharmacokinetic parameters were higher than those of GP at the same dosage, which showed that GPA was likely to be the main absorbed saponin in vivo. These findings provide useful information that will support the studies on identification of bioactive platycosides in vivo, and will lay the foundation for the development of Jiegeng.