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However, its distribution and metabolic characteristics have not been fully elucidated in\u00a0vivo. In this study, ultra\u2010high liquid chromatography tandem high\u2010resolution mass spectrometry (UHPLC\u2010HRMS\/MS) was used to investigate the pharmacokinetic characteristics and effects of cordycepin on endogenous adenosine and inosine. Microdialysis was used for real\u2010time 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\u2009&gt;\u2009liver\u2009&gt;\u2009heart\u2009&gt;\u2009lung\u2009&gt;\u2009spleen\u2009&gt;\u2009brain. 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\u2032\u2010deoxyinosine was generated as the main metabolite. The <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub> values of cordycepin in the rat blood and brain after exposure (10\u2009mg\/kg, i.p.) were 7.8 and 5.4\u2009ng\/mL, respectively. Mean residence time in blood and brain was 102.2 and 137.0\u2009min, respectively. Inhibition of adenosine deaminase by racemic 9\u2010(2\u2010hydroxy\u20103\u2010nonyl) 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.<\/jats:p>","DOI":"10.1002\/bmc.70038","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T08:30:37Z","timestamp":1741768237000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Distribution and Pharmacokinetic Characteristics of Cordycepin in Rat: Investigated by UHPLC\u2010HRMS\/MS and Blood\u2013Brain Synchronous Microdialysis"],"prefix":"10.1002","volume":"39","author":[{"given":"Mengjiao","family":"Li","sequence":"first","affiliation":[{"name":"Flavour Science Research Center, College of Chemistry Zhengzhou University  Zhengzhou China"},{"name":"Beijing Life Science Academy (BLSA)  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuqiang","family":"Liu","sequence":"additional","affiliation":[{"name":"Flavour Science Research Center, 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