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

  • Biomed Chromatogr. 2025 Apr;39(4):e70038. doi: 10.1002/bmc.70038.
Mengjiao Li  1  2 ,  Fuqiang Liu  1  2 ,  Lulu Guo  2 ,  Wu Fan  3 ,  Jiazhong Wang  2 ,  Binbin Lu  3 ,  Guangfeng Hong  3 ,  Wenjuan Zhang  3 ,  Shu Tian  4 ,  Jian Mao  1  2  3 ,  Jianping Xie  1  2
Affiliations
  • 1. Flavour Science Research Center, College of Chemistry, Zhengzhou University, Zhengzhou, China.
  • 2. Beijing Life Science Academy (BLSA), Beijing, China.
  • 3. Zhengzhou Tobacco Research Institute of China National Tobacco Company, Zhengzhou, China.
  • 4. Inner Mongolia Kunming Cigarette Limited Liability Company, Huhhot, China.
PMID: 40071940 DOI: 10.1002/bmc.70038
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 Cmax 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.

Keywords
UHPLC‐HRMS/MS; cordycepin; distribution; microdialysis; pharmacokinetics.
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