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Synthesis, pharmacokinetic studies, and metabolite analysis of meridianin C in rats using a validated ultra high performance liquid chromatography-tandem mass spectrometry method

Year: 2025

Type: article

Abstract: Introduction Meridianin C (MC) is a marine-derived indole alkaloid that has demonstrated kinase inhibitory and anti-tumor activities. Despite its diverse biological properties, no previous reports have systematically evaluated the in vivo quantitative analysis of MC and its metabolites. Methods In this study, MC was synthesized following a previously reported procedure with slight modifications. A sensitive, accurate, and reliable ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC–MS/MS) method was developed to simultaneously detect MC and its five major metabolites (MC-1-N-O-GluA, MC-1-N-O-SO3H, MC-2′-N-O-GluA, MC-2′-N-O-SO3H, and MC-O-GluA-didehydration) in rat plasma. Rats received a single oral dose of MC (100 mg/kg), and pharmacokinetic analysis was subsequently performed. Results Pharmacokinetic data revealed that MC was rapidly absorbed, with a Cmax of 44.8 ± 7.0 μmol/L, an AUC0–48h of 232.0 ± 85.9 μmol·h/L, a Tmax of 0.75 ± 0.27 h, and a t1/2 of 17.7 ± 14.1 h. Plasma concentrations of MC were significantly higher than those of its metabolites, suggesting that MC remains the predominant circulating form after oral administration. The identified metabolites mainly resulted from hydroxylation combined with glucuronide conjugation, hydroxylation combined with sulfation, and hydration combined with glucuronide conjugation. Discussion These findings demonstrate that the primary metabolic pathway of MC involves hydroxylation (phase I) followed by conjugation (phase II). To our knowledge, this represents the first systematic investigation of the pharmacokinetic characteristics of MC and its metabolites in rats. The study not only advances understanding of MC disposition but also provides a valuable reference for future pharmacokinetic evaluations of other marine-derived indole alkaloids.

Source: Frontiers in Pharmacology

DOI: 10.3389/fphar.2025.1633157

Authors: Liangyu Xu, Zhaogen Wu, Karna Ramachandraiah, Guihun Jiang, Guozhe Zhang

Institutions: Jilin Medical University, Louisiana State University Health Sciences Center New Orleans

Language: English

Topic: Analytical Methods in Pharmaceuticals

Subfield: Analytical Chemistry

Field: Chemistry

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801