ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Pharmacology of Anti-Cancer Drugs
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1633157
This article is part of the Research TopicIntegrated PK/PD and Drug Metabolism Approaches in Drug Development and EvaluationView all 5 articles
Synthesis, pharmacokinetic studies, and metabolite analysis of meridianin C in rats using a validated ultra high performance liquid chromatography-tandem mass spectrometry method
Provisionally accepted
- 1Jilin Medical University, Jilin, China
- 2University of North Florida, Jacksonville, United States
- 3Jiangsu Vocational College of Medicine, Jiangsu, China
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Meridianin C (MC) is a marine-derived indole alkaloid known for its kinase inhibitory and antitumor activities. Although MC exhibits diverse biological activities, there have been no previous reports on the quantitative analysis of MC and its metabolites in vivo. In this study, MC was synthesized using a previously reported procedure with minor modifications. In order to evaluate the pharmacokinetic profiles of MC and its five main metabolites, (MC-1a sensitive, accurate and reliable ultra high performance liquid chromatography-tandem mass spectrometry approach was established for the detection of these compounds in rat plasma. Following a single oral administration of MC (100 mg/kg) to rats, pharmacokinetic analysis showed 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. The plasma concentrations of MC were substantially higher than those of its major metabolites, indicating that MC is the predominant circulating form after oral dosing. All of the five metabolites detected were based on hydroxylation + glucuronide conjugation, hydroxylation + sulfation and hydration + glucuronide conjugation. These results indicate that the main metabolic route of MC involves hydroxylation in phase I followed by conjugation in phase II. This is the first systematic study focusing on the pharmacokinetic profiles of MC and its metabolites in rats. Therefore, this study will likely contribute to the development of drugs using MC and also provide a reference for future pharmacokinetic studies of other indole alkaloids.
Keywords: Meridianin C1, indole alkaloid2, synthesis3, metabolites4, pharmacokinetics5, UHPLC-MS/MS5
Received: 12 Jun 2025; Accepted: 27 Aug 2025.
Copyright: © 2025 Xu, Ramachandraiah, Wu, Jiang and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Guihun Jiang, Jilin Medical University, Jilin, China
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