{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T03:12:35Z","timestamp":1785553955907,"version":"3.56.0"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T00:00:00Z","timestamp":1752105600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec><jats:title>Introduction:<\/jats:title><jats:p>Ginsenoside Rh3 (GRh<jats:sub>3<\/jats:sub>), a rare ginsenoside, demonstrates diverse pharmacological activities <jats:italic>in vitro<\/jats:italic>; however, the lack of pharmacokinetic and tissue distribution data has limited its translation to <jats:italic>in vivo<\/jats:italic> applications. This study aimed to develop and validate a novel liquid chromatography-tandem mass spectrometry (LC-MS\/MS) method for quantifying GRh<jats:sub>3<\/jats:sub> in rat biological matrices and to characterize its pharmacokinetic profile and tissue distribution following oral administration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods:<\/jats:title><jats:p>A validated LC-MS\/MS method was established for the quantification of GRh<jats:sub>3<\/jats:sub> in rat plasma and tissues. Male Sprague-Dawley rats received an oral dose of GRh<jats:sub>3<\/jats:sub> (100 mg\/kg), and plasma samples were collected up to 72 h post-dose for pharmacokinetic analysis. Tissue samples (intestine, stomach, liver, brain, etc.) were collected at the time corresponding to the maximum plasma concentration for distribution analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results:<\/jats:title><jats:p>The LC-MS\/MS method showed excellent precision, accuracy, and extraction recovery (\u2265 85%), with minimal matrix effects. GRh<jats:sub>3<\/jats:sub> exhibited a prolonged elimination half-life (14.7 \u00b1 1.7 h), a low clearance rate (13.0 \u00b1 3.8 L\/h\/kg), and a high volume of distribution (280.4 \u00b1 109.3 L\/kg). Tissue distribution analysis revealed the highest GRh<jats:sub>3<\/jats:sub> concentrations in the intestine (15445.2 ng\/g), followed by the stomach (2906.7 ng\/g) and liver (1930.8 ng\/g). Notably, GRh<jats:sub>3<\/jats:sub> was able to cross the blood-brain barrier, with significant accumulation observed in the hippocampus (520.0 ng\/g).<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion:<\/jats:title><jats:p>The prolonged elimination and extensive tissue distribution of GRh<jats:sub>3<\/jats:sub>, particularly its ability to penetrate the brain, indicate potential therapeutic benefits or neurotoxic risks involving the central nervous system. The mechanism underlying its blood-brain barrier permeability warrants further investigation, potentially involving transporter-mediated uptake or modulation of barrier integrity. These findings provide a foundation for optimizing GRh<jats:sub>3<\/jats:sub> dosing regimens and guiding future preclinical studies.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphar.2025.1582644","type":"journal-article","created":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T07:26:47Z","timestamp":1752132407000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Pharmacokinetics and tissue distribution analysis of ginsenoside Rh3 in rats using a novel LC-MS\/MS quantification strategy"],"prefix":"10.3389","volume":"16","author":[{"given":"Cong","family":"Hu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuheng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peifang","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,7,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"102516","DOI":"10.1016\/j.mex.2023.102516","article-title":"Rodent brain extraction and dissection: a comprehensive approach","volume":"12","author":"Aboghazleh","year":"2024","journal-title":"MethodsX"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.5142\/jgr.2013.37.1","article-title":"The world ginseng market and the ginseng (korea)","volume":"37","author":"Baeg","year":"2013","journal-title":"J. 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