Simultaneous determination of valproic acid and 2-propyl-4-pentenoic acid for the prediction of clinical adverse effects in Chinese patients with epilepsy
Simultaneous determination of valproic acid and 2-propyl-4-pentenoic acid for the prediction of clinical adverse effects in Chinese patients with epilepsy
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DOI：
10.1016/j.seizure.2011.10.002
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发表时间：
2012-03
期刊：
影响因子：
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通讯作者：
Zhuojia Chen;Xueding Wang;Hong-Sheng Wang;Shu-da Chen;Liemin Zhou;Jia-Li Li-Jia-Li-Li-119582029;Wen-ying Shu;Jue-qian Zhou;Z. Fang;Yu Zhang;Min Huang
中科院分区：
文献类型：
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作者：
Zhuojia Chen;Xueding Wang;Hong-Sheng Wang;Shu-da Chen;Liemin Zhou;Jia-Li Li-Jia-Li-Li-119582029;Wen-ying Shu;Jue-qian Zhou;Z. Fang;Yu Zhang;Min Huang
丙戊酸（VPA）是一种成熟的抗惊厥药物，已越来越多地用于治疗多种形式的全身性癫痫。尽管有许多关于VPA不良反应的报告，但关注VPA及其代谢产物在癫痫患者中的浓度-反应关系的研究非常有限。本研究以2，4 ′-二溴苯乙酮为衍生试剂，辛酸为内标物，建立了一种快速、专属性强的高效液相色谱-紫外（HPLC-UV）法同时测定人血浆中丙戊酸及其主要肝毒性代谢物2-丙基-4-戊烯酸（4-ene VPA）浓度。用该方法分析了64例癫痫患者的血浆样品。结果显示，中国患者的4-烯VPA浓度远高于美国和伊朗等其他国家的患者。天门冬氨酸氨基转移酶（AST）、丙氨酸氨基转移酶（ALT）与4-烯VPA浓度之间的显著相关性表明，同时测定VPA和4-烯VPA是预测癫痫患者临床肝毒性的有效工具。此外，本研究描述了一种成本较低且复杂的技术，用于临床监测VPA血浆水平和肝毒性风险，这可能是中国等发展中国家特别感兴趣的。
Valproic acid (VPA) is a well-established anticonvulsant drug that has been increasingly used in the treatment of many forms of generalized epilepsy. Although there are many reports of adverse effects of VPA, studies focusing on the concentration–response relationships of VPA and its metabolites in patients with epilepsy are extremely limited. In this study, a rapid and specific high performance liquid chromatography-ultraviolet (HPLC-UV) method to simultaneously detect the concentrations of VPA and its major hepatotoxic metabolite 2-propyl-4-pentenoic acid (4-ene VPA) in human plasma has been established, using 2,4′-dibromoacetophenone and octanoic acid as the derivatization reagent and internal standard, respectively. This method was used to analyze plasma samples (n=64) of Chinese patients with epilepsy. The results revealed that 4-ene VPA concentrations in Chinese patients were much higher than those in patients in other countries such as United States and Iran. Significant correlations between aspartate aminotransferase (AST), alanine aminotransferase (ALT) and 4-ene VPA concentration suggest that the simultaneous determination of VPA and 4-ene VPA is an effective tool for the prediction of clinical hepatotoxicity in epileptic patients. Furthermore, the present study describes a less costly and complex technique for the clinical monitoring of VPA plasma levels and the risk of hepatotoxicity which may be of particular interest in developing countries like China.