ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Drugs Outcomes Research and Policies
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1592731
A Sex-Sensitive LC-MS/MS Method with Isotopic Internal Standard for Prazosin Bioequivalence: Bridging Precision Medicine and Generic Drug Policy in China
Provisionally accepted
- 1Changsha Stomatological Hospital, Changsha, China
- 2Hubei Provincial Corps Hospital, Chinese People’s Armed Police Forces, Hubei, China
- 3Xiangya Boai Rehabilitation Hospital, Changsha, China
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Objective: To develop a rapid, sensitive, and high-throughput liquid chromatographytandem 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.Materials and Methods: Plasma samples were processed by protein precipitation with methanol and analyzed using a Waters ACQUITY UPLC® 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 mL/min. Quantification was achieved using positive ionization mode with multiple reaction monitoring (MRM) transitions of m/z 384.2→95.0 for prazosin and m/z 392.2→95.0 for IS.The method demonstrated excellent linearity (0.1000-30.00 ng/mL, LLOQ: 0.1000 ng/mL), surpassing the sensitivity of prior methods. Bioequivalence analysis confirmed that the 90% confidence interval (CI) for AUC0-24, AUC0-∞, and Cmax geometric mean ratios fell within the regulatory acceptance range (90.00%-111.11%).Sex analysis revealed significantly higher AUC0-24 (+48%) and AUC0-∞ (+46%) medians in females (n=4) than in males (n=16) (P < 0.05), suggesting potential sexbased differences in prazosin pharmacokinetics.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's generic drug policy and highlight the need for sex-stratified pharmacokinetic evaluations in bioequivalence assessments.
Keywords: Prazosin, Prazosin-d8, LC-MS/MS, pharmacokinetics, Bioequivalence
Received: 13 Mar 2025; Accepted: 14 May 2025.
Copyright: © 2025 Chen, Guo, Zhu, Haung and Guo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Jincai Guo, Changsha Stomatological Hospital, Changsha, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.