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Liquid chromatography–tandem mass spectrometry method for simultaneous determination of valproic acid and its ene-metabolites in epilepsy patient plasma

查看全文 作  者:Huan [1]Lu;Chong [2]Su;Lei [2,3]Yin;Liqiang [1]Gu;Jingkai [2,3]Gu;Xiaohui [1]Chen 高影响力作者 机构地区:[1]School of Pharmacy,Shenyang Pharmaceutical University;[2]Research Center for Drug Metabolism,College of Life Science,Jilin University;[3]Clinical Pharmacology Center, Research Institute of Translational Medicine, the First Hospital of Jilin University高影响力机构 出  处:《Journal of Pharmaceutical Analysis》索引2016年第6卷第2期,共5页高影响力期刊 摘  要:A simple and high throughput method was developed and validated for simultaneous determination of valproic acid and its two toxicant ene-metabolites, 2-enevalproic acid and 4-enevalproic acid in epilepsy patient plasma using liquid chromatography–tandem mass spectrometry. Probenecid was used as internal standard and solid-phase extraction was selected for sample preparation. A chromatographic separation was performed on an Agilent Poroshell SB-C_(18) column(50 mm*4.6 mm i.d., 2.7 μm) by an optimized gradient elution at a flow rate of 0.9 mL/min. The total run time was 7 min. Electrospray ionization was used in negative ion mode by multiple reaction monitoring of the precursor-to-product ion transitions at m/z 143.0→143.0 for valproic acid, m/z 140.9→140.9 for 2-enevalproic acid and 4-enevalproic acid for their poor fragments, and m/z 283.9→239.9 for probenecid. The results showed good linearity of valproic acid, 2-enevalproic acid and 4-enevalproic acid in their respective linear ranges.The correlation coef fi cients were more than 0.998. The intra- and inter-day precision of the assay was less than 11.0% and the accuracy ranged from 2% to 12%. This analytical method was successfully applied to assay plasma concentrations of valproic acid and its two ene-metabolites in epilepsy patient plasma and used for therapeutic drug monitoring. 关 键 词:液相色谱-串联质谱法 血浆浓度 同时测定 代谢物 戊酸 患者 癫痫 多反应监测
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