Sun Jinchun, Schnackenberg Laura K, Hansen Deborah K, Beger Richard D
Division of Systems Toxicology, National Center for Toxicological Research, US FDA, Jefferson, AR, USA.
Bioanalysis. 2010 Feb;2(2):207-16. doi: 10.4155/bio.09.173.
Valproic acid (VPA; an anticonvulsant drug) therapy is associated with hepatotoxicity as well as renal toxicity. An LC-MS-based metabolomics approach was undertaken in order to detect urinary VPA metabolites and to discover early biomarkers of the adverse effects induced by VPA.
CD-1 mice were either subcutaneously injected with 600-mg VPA/kg body weight or vehicle only, and urine samples were collected at 6, 12, 24 and 48 h postinjection. A metabolomics approach combined with principal component analysis was utilized to identify VPA-related metabolites and altered endogenous metabolites in urine. Some VPA metabolites indicated potential liver toxicity caused by VPA administration. Additionally, some altered endogenous metabolites suggested that renal function might be perturbed by VPA dosing.
LC-MS-based metabolomics is capable of rapidly profiling VPA drug metabolites and is a powerful tool for the discovery of potential early biomarkers related to perturbations in liver and kidney function.
丙戊酸（VPA；一种抗惊厥药物）治疗与肝毒性以及肾毒性相关。采用基于液相色谱-质谱联用的代谢组学方法来检测尿液中的VPA代谢物，并发现由VPA诱导的不良反应的早期生物标志物。
给CD-1小鼠皮下注射600mg VPA/kg体重或仅注射溶剂，在注射后6、12、24和48小时收集尿液样本。利用代谢组学方法结合主成分分析来鉴定尿液中与VPA相关的代谢物和变化的内源性代谢物。一些VPA代谢物表明VPA给药引起潜在的肝毒性。此外，一些变化的内源性代谢物表明VPA给药可能会扰乱肾功能。
基于液相色谱-质谱联用的代谢组学能够快速分析VPA药物代谢物，是发现与肝肾功能紊乱相关的潜在早期生物标志物的有力工具。
