A sex-sensitive LC-MS/MS method with isotopic internal standard for prazosin bioequivalence: bridging precision medicine and generic drug policy in China
ObjectiveTo 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 populati...
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| Format: | Article |
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Frontiers Media S.A.
2025-05-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1592731/full |
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| author | Hui Chen Hui Chen Junping Guo Zhenyu Zhu Xiaomei Huang Jincai Guo Jincai Guo |
| author_facet | Hui Chen Hui Chen Junping Guo Zhenyu Zhu Xiaomei Huang Jincai Guo Jincai Guo |
| author_sort | Hui Chen |
| collection | DOAJ |
| description | ObjectiveTo 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.Materials and methodsPlasma 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.ResultsThe 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 sex-based differences in prazosin pharmacokinetics.ConclusionThis 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.Clinical trial registration numberChiCTR2100050626. |
| format | Article |
| id | doaj-art-9e1f6145fbc64c04945c2ef4c3dd08da |
| institution | Kabale University |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-9e1f6145fbc64c04945c2ef4c3dd08da2025-08-20T03:53:56ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-05-011610.3389/fphar.2025.15927311592731A sex-sensitive LC-MS/MS method with isotopic internal standard for prazosin bioequivalence: bridging precision medicine and generic drug policy in ChinaHui Chen0Hui Chen1Junping Guo2Zhenyu Zhu3Xiaomei Huang4Jincai Guo5Jincai Guo6Department of Pharmacy, Changsha Stomatological Hospital, Changsha, ChinaSchool of Stomatology, Hunan University of Chinese Medicine, Changsha, ChinaDepartment of Pharmacy, Hubei Province Corps Hospital, The Chinese Armed Police Force (CAPF), Wuhan, ChinaDepartment of Phase I Clinical Trial Research Center, XiangYa BoAi Rehabilitation Hospital, Changsha, ChinaDepartment of Phase I Clinical Trial Research Center, XiangYa BoAi Rehabilitation Hospital, Changsha, ChinaDepartment of Pharmacy, Changsha Stomatological Hospital, Changsha, ChinaSchool of Stomatology, Hunan University of Chinese Medicine, Changsha, ChinaObjectiveTo 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.Materials and methodsPlasma 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.ResultsThe 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 sex-based differences in prazosin pharmacokinetics.ConclusionThis 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.Clinical trial registration numberChiCTR2100050626.https://www.frontiersin.org/articles/10.3389/fphar.2025.1592731/fullprazosinprazosin-d8LC-MS/MSpharmacokineticsbioequivalence |
| spellingShingle | Hui Chen Hui Chen Junping Guo Zhenyu Zhu Xiaomei Huang Jincai Guo Jincai Guo A sex-sensitive LC-MS/MS method with isotopic internal standard for prazosin bioequivalence: bridging precision medicine and generic drug policy in China Frontiers in Pharmacology prazosin prazosin-d8 LC-MS/MS pharmacokinetics bioequivalence |
| title | A sex-sensitive LC-MS/MS method with isotopic internal standard for prazosin bioequivalence: bridging precision medicine and generic drug policy in China |
| title_full | A sex-sensitive LC-MS/MS method with isotopic internal standard for prazosin bioequivalence: bridging precision medicine and generic drug policy in China |
| title_fullStr | A sex-sensitive LC-MS/MS method with isotopic internal standard for prazosin bioequivalence: bridging precision medicine and generic drug policy in China |
| title_full_unstemmed | A sex-sensitive LC-MS/MS method with isotopic internal standard for prazosin bioequivalence: bridging precision medicine and generic drug policy in China |
| title_short | A sex-sensitive LC-MS/MS method with isotopic internal standard for prazosin bioequivalence: bridging precision medicine and generic drug policy in China |
| title_sort | sex sensitive lc ms ms method with isotopic internal standard for prazosin bioequivalence bridging precision medicine and generic drug policy in china |
| topic | prazosin prazosin-d8 LC-MS/MS pharmacokinetics bioequivalence |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1592731/full |
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