{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T05:51:22Z","timestamp":1768542682364,"version":"3.49.0"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,23]],"date-time":"2025-05-23T00:00:00Z","timestamp":1747958400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To develop a rapid, sensitive, and high-throughput liquid chromatography-tandem mass spectrometry (LC-MS\/MS) method for prazosin quantification in human plasma, validate its application in bioequivalence studies, and investigate sex-specific pharmacokinetic differences in a Chinese population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>Plasma samples were processed by protein precipitation with methanol and analyzed using a Waters ACQUITY UPLC<jats:sup>\u00ae<\/jats:sup> HSS T3 column. Prazosin-d8 was used as an isotopic internal standard (IS) to enhance quantification accuracy. Chromatographic separation was performed with methanol (A) and 0.1% formic acid in water (B) as the mobile phases, using gradient elution at 0.35\u00a0mL\/min. Quantification was achieved using positive ionization mode with multiple reaction monitoring (MRM) transitions of m\/z 384.2\u219295.0 for prazosin and m\/z 392.2\u219295.0 for IS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The method demonstrated excellent linearity (0.1000\u201330.00\u00a0ng\/mL, LLOQ: 0.1000\u00a0ng\/mL), surpassing the sensitivity of prior methods. Bioequivalence analysis confirmed that the 90% confidence interval (CI) for AUC<jats:sub>0-24<\/jats:sub>, AUC<jats:sub>0-\u221e<\/jats:sub>, and C<jats:sub>max<\/jats:sub> geometric mean ratios fell within the regulatory acceptance range (90.00%\u2013111.11%). Sex analysis revealed significantly higher AUC<jats:sub>0-24<\/jats:sub> (+48%) and AUC<jats:sub>0-\u221e<\/jats:sub> (+46%) medians in females (n = 4) than in males (n = 16) (<jats:italic>P<\/jats:italic> &amp;lt; 0.05), suggesting potential sex-based differences in prazosin pharmacokinetics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study establishes the first LC-MS\/MS method integrating isotopic IS and sex-specific pharmacokinetic profiling for prazosin, offering regulatory-compliant bioequivalence validation and insights into precision dosing strategies. These findings support China\u2019s generic drug policy and highlight the need for sex-stratified pharmacokinetic evaluations in bioequivalence assessments.<\/jats:p><\/jats:sec><jats:sec><jats:title>Clinical trial registration number<\/jats:title><jats:p>ChiCTR2100050626.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphar.2025.1592731","type":"journal-article","created":{"date-parts":[[2025,5,23]],"date-time":"2025-05-23T05:29:31Z","timestamp":1747978171000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["A sex-sensitive LC-MS\/MS method with isotopic internal standard for prazosin bioequivalence: bridging precision medicine and generic drug policy in China"],"prefix":"10.3389","volume":"16","author":[{"given":"Hui","family":"Chen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junping","family":"Guo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenyu","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaomei","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jincai","family":"Guo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,5,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1007\/s002280050067","article-title":"The effect of aging on the pharmacokinetics and pharmacodynamics of prazosin","volume":"50","author":"Andros","year":"1996","journal-title":"Eur. 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