摘要
目的:建立同时测定人血浆中丙戊酸钠(VPA)及其代谢产物2-丙基-2-戊烯酸(2-ene-VPA)浓度的方法。方法:血浆样品经环己烷沉淀蛋白后,用2,4'-二溴苯乙酮进行衍生化,以正辛酸为内标,采用反相高效液相色谱法测定。色谱柱为Zorbax SB-C_(18),流动相为乙腈-水(65:35,V/V),流速为1 mL/min,柱温为35℃,紫外检测波长为258 nm,进样量为20μL。结果:VPA、2-ene-VPA血药浓度分别在5.0~200.0、0.5~20.0μg/mL范围内线性关系良好(r均为0.999 9,n=5),定量下限分别为5.0、0.5μg/mL;日内、日间RSD均小于5%,方法回收率分别为95.99%~98.80%、97.40%~98.17%,提取回收率分别为80.46%~86.23%、80.45%~85.61%。采用该法测得10例癫痫患儿VPA血药浓度为27.4~93.2μg/mL,2-ene-VPA血药浓度为0.85~3.94μg/mL。结论:该方法操作简便、专属性强,可用于VPA血药浓度检测及药动学研究。
OBJECTIVE：To establish a method for simultaneous determination of sodium valproate（VPA） and its metabolite 2-propyl-2-pentenoic acid（2-ene-VPA） in human plasma.METHODS：Plasma sample was extracted with cyclohexane and experienced derivatization with 2,4＇-dibromoacetophenone using n-octanoic acid as an internal standard.RP-HPLC method was adopted.The determination was performed on Zorbax SB-C（18） column with mobile phase consisted of acetonitrile-water（65：35,V/V） at the flow rate of 1 mL/min.The column temperature was set at 35℃,and UV dectection wavelenth was set at 258 nm.The sample size was 20 μL.RESULTS：The linear range of VPA and 2-ene-VPA were 5.0-200.0,0.5-20.0 μg/mL（r=0.999 9,n=5）.The limits of quantification were 5.0,0.5 μg/mL.RSDs of inter-day and intra-day were all lower than 5%.Method recoveries were 95.99%-98.80%and 97.40%-98.17%,and extraction recoveries were 80.46%-86.23%and 80.45%-85.61%.The plasma concentrations of VPA in 10 epileptic children were 27.4-93.2 μg/mL,and those of 2-ene-VPA were 0.85-3.94 μg/mL,respectively.CONCLUSIONS：The method is simple,specific and suitable for plasma concentration determination and pharmacokinetic study of VPA.
出处
《中国药房》
CAS
北大核心
2017年第5期611-614,共4页
China Pharmacy
基金
贵州省卫生计生委科学技术基金项目(No.gzwjkj2015-1-076)
