{"title":"Simultaneous Determination of Levetiracetam, Sodium Valproate, and Olanzapine in Human Plasma by UPLC-MS/MS for Therapeutic Drug Monitoring","authors":"Feng Zhou, Xinjun Cai, Chongyang Wu","doi":"10.1002/bmc.70536","DOIUrl":null,"url":null,"abstract":"<div>\n \n <p>Levetiracetam, sodium valproate, and olanzapine are widely used for epilepsy, but their therapeutic windows and pharmacokinetic variability require TDM. No existing method enables their simultaneous quantification. This study aimed to establish and validate a UPLC-MS/MS method for their simultaneous detection in human plasma. Plasma samples were processed by protein precipitation. Chromatographic separation was achieved with gradient elution (3.0 min total time), and MRM mode was used for detection. The method showed good linearity (<i>R</i> ≥ 0.9956), precision (CV ≤ 7.27%), and accuracy (bias: −8.95% ~ 9.17%). Extraction recoveries were 94.56%–103.98%, with negligible matrix effects. Application to 136 patients showed average concentrations within therapeutic ranges. This UPLC-MS/MS method is rapid, accurate, and suitable for routine TDM of the three drugs, providing a reliable tool for individualized pharmacotherapy.</p>\n </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"40 8","pages":""},"PeriodicalIF":1.7000,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biomedical Chromatography","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/bmc.70536","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}
引用次数: 0
Abstract
Levetiracetam, sodium valproate, and olanzapine are widely used for epilepsy, but their therapeutic windows and pharmacokinetic variability require TDM. No existing method enables their simultaneous quantification. This study aimed to establish and validate a UPLC-MS/MS method for their simultaneous detection in human plasma. Plasma samples were processed by protein precipitation. Chromatographic separation was achieved with gradient elution (3.0 min total time), and MRM mode was used for detection. The method showed good linearity (R ≥ 0.9956), precision (CV ≤ 7.27%), and accuracy (bias: −8.95% ~ 9.17%). Extraction recoveries were 94.56%–103.98%, with negligible matrix effects. Application to 136 patients showed average concentrations within therapeutic ranges. This UPLC-MS/MS method is rapid, accurate, and suitable for routine TDM of the three drugs, providing a reliable tool for individualized pharmacotherapy.
期刊介绍：
Biomedical Chromatography is devoted to the publication of original papers on the applications of chromatography and allied techniques in the biological and medical sciences. Research papers and review articles cover the methods and techniques relevant to the separation, identification and determination of substances in biochemistry, biotechnology, molecular biology, cell biology, clinical chemistry, pharmacology and related disciplines. These include the analysis of body fluids, cells and tissues, purification of biologically important compounds, pharmaco-kinetics and sequencing methods using HPLC, GC, HPLC-MS, TLC, paper chromatography, affinity chromatography, gel filtration, electrophoresis and related techniques.
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