Metabolic Profiling of 5-Methoxypinocembroside and Pharmacokinetics Study of Its Major Metabolite Alpinetin in Rat Plasma by UHPLC-MS

5-Methoxypinocembroside (5-MP), a key bioactive compound isolated from Penthrum chinense Pursh (PCP), has demonstrated a specific pharmacological effect against hepatic steatosis. However, its metabolism and pharmacokinetics remain unexplored. In this study, rats were administered 5-MP intragastrically at a dose of 25 mg/kg, and blood samples were collected and processed for analysis. Ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS) was employed to identify plasma metabolites of 5-MP, and its pharmacokinetics in rats were further evaluated. A total of 20 metabolites were characterized, including those formed via demethylation, sulfation, and deglycosylation. Among these, the aglycone alpinetin (ALP) was identified as the predominant metabolite of 5-MP. The pharmacokinetic analysis of ALP revealed a maximum plasma concentration (C_max) of 70.7 ± 44.4 ng/mL, with a peak time (T_max) of 0.4 ± 0.5 h. The area under the concentration-time curve from zero to the last measurable concentration (AUC_{0 - t}) was 266.7 ± 146.2 μg/L·h. This study is the first to elucidate the metabolic profile of 5-MP in rats and to characterize the pharmacokinetics of ALP as its primary metabolite.

5‐methoxypinocembroside; Penthorum chinense Pursh; metabolites identification; pharmacokinetics.