Distribution and Pharmacokinetic Characteristics of Cordycepin in Rat: Investigated by UHPLC-HRMS/MS and Blood–Brain Synchronous Microdialysis

IF 1.8 4区医学 Q4 BIOCHEMICAL RESEARCH METHODS Biomedical Chromatography Pub Date : 2025-03-12 DOI:10.1002/bmc.70038

Mengjiao Li, Fuqiang Liu, Lulu Guo, Wu Fan, Jiazhong Wang, Binbin Lu, Guangfeng Hong, Wenjuan Zhang, Shu Tian, Jian Mao, Jianping Xie

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引用次数: 0

Abstract

Cordycepin, a natural adenosine derivative, exhibits multiple pharmacological effects on organisms. However, its distribution and metabolic characteristics have not been fully elucidated in vivo. In this study, ultra-high liquid chromatography tandem high-resolution mass spectrometry (UHPLC-HRMS/MS) was used to investigate the pharmacokinetic characteristics and effects of cordycepin on endogenous adenosine and inosine. Microdialysis was used for real-time monitoring of unbound drug in brain and blood, whereas conventional tissue homogenate methods assessed distribution in various tissues. Results showed that the distribution pattern of cordycepin was as follows: kidney > liver > heart > lung > spleen > brain. Cordycepin administration significantly altered the levels of adenosine and inosine in heart and liver. Synchronous microdialysis sampling for the pharmacokinetic profile indicated that cordycepin was rapidly consumed and 3′-deoxyinosine was generated as the main metabolite. The C_max values of cordycepin in the rat blood and brain after exposure (10 mg/kg, i.p.) were 7.8 and 5.4 ng/mL, respectively. Mean residence time in blood and brain was 102.2 and 137.0 min, respectively. Inhibition of adenosine deaminase by racemic 9-(2-hydroxy-3-nonyl) adenine hydrochloride (EHNA) enhanced cordycepin levels in the blood. This work provides a solid basis for understanding the metabolism of cordycepin and its pharmacological effects.

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来源期刊

Biomedical Chromatography 生物-分析化学

CiteScore

3.60

自引率

5.60%

发文量

268

审稿时长

2.3 months

期刊介绍： Biomedical Chromatography is devoted to the publication of original papers on the applications of chromatography and allied techniques in the biological and medical sciences. Research papers and review articles cover the methods and techniques relevant to the separation, identification and determination of substances in biochemistry, biotechnology, molecular biology, cell biology, clinical chemistry, pharmacology and related disciplines. These include the analysis of body fluids, cells and tissues, purification of biologically important compounds, pharmaco-kinetics and sequencing methods using HPLC, GC, HPLC-MS, TLC, paper chromatography, affinity chromatography, gel filtration, electrophoresis and related techniques.