ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Drug Metabolism and Transport
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1595731
Integrated UPLC-MS/MS and UPLC-Q-TOF-MS/MS analysis to reveal pharmacokinetics, tissue distribution, metabolism, and excretion of sipeimine in rats
Provisionally accepted
Hui Zong1Chongyang Wang1Dongdong He1Liting Liu1Juanjuan Wan1Guodong Wang1Dingtao Li1Jun Ran1Meiling Zhang2
Hui Tang1
Liping Wang1*- 1School of Pharmacy, Shihezi University, Shihezi, China
- 2Shihezi Institute for Drug Control, Shihezi, China
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Background and Objective: Fritillaria Bulbus is a traditional Chinese medicine used to treat respiratory diseases such as cough, expectoration, and asthma for more than 2000 years. Sipeimine, a major isosteroidal alkaloid isolated from Fritillaria Bulbus, has attracted considerable attention from the research community owing to its antitussive, anti-inflammatory, and lung-protective activities. However, there exist few reports regarding the in vivo disposition of sipeimine. This study aims to investigate the disposition of sipeimine in rats.Methods: A rapid, sensitive, and selective UPLC-MS/MS approach was developed to the quantification of sipeimine in various biological samples and successfully applied to the investigation of pharmacokinetic characteristics, tissue distribution, and excretion of sipeimine in rats. A reliable UPLC-Q-TOF-MS/MS combined with a scientific metabolite identification strategy was used to characterize the metabolic transformation of sipeimine in rat plasma and urine.Results: The established UPLC-MS/MS method was accurate and reliable with a good linearity (r 2 > 0.99) in the respective concentration range, satisfying the quantitative requirements. Sipeimine exhibited the characteristics of rapid absorption and slow elimination in rats, with an average oral bioavailability of 40%. Furthermore, sipeimine was rapidly distributed in all the organs except brain, and the plasma protein binding ratio of sipeimine was found to be approximately 30%. The metabolism of sipeimine in rats is chiefly accomplished via its hydroxylation, sulfation, and glucose conjugation. Analysis of fecal and urinary samples revealed that sipeimine is predominantly excreted unchanged via renal elimination.The pharmacokinetics, tissue distribution, metabolism, and excretion of sipeimine were comprehensively characterized and elucidated. These results are expected to prove useful for the interpretation of the pharmacokinetic and pharmacodynamic characteristics of sipeimine and the traditional Chinese medicines containing sipeimine.
Keywords: Sipeimine, pharmacokinetics, Tissue Distribution, Metabolism, excretion
Received: 18 Mar 2025; Accepted: 19 May 2025.
Copyright: © 2025 Zong, Wang, He, Liu, Wan, Wang, Li, Ran, Zhang, Tang and Wang. 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: Liping Wang, School of Pharmacy, Shihezi University, Shihezi, China
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