摘要
癫痫是神经系统的一种常见病,不少患者需长期同时服用两种或两种以上抗癫痫药物.本研究采用高效液相色谱-电喷雾离子化质谱法同时测定5种常用抗癫痫药物卡马西平、氯硝西泮、阿普唑仑、艾司唑仑和苯妥英钠的血药浓度,色谱条件为以地西泮作为内标,Zorbax SB-C18(30mm×2.1mm,3.5μm)为色谱柱,甲醇-25mM的乙酸铵水溶液梯度洗脱,样品采用无水乙醚萃取.样品分析以离子阱质谱作为检测器,采用多重反应监测模式(MRM),选择MS2离子提高方法的专属性,5种抗癫痫药物在50~5000ng/mL浓度范围内均具有良好的线性关系,其日内、日间精密度均小于10%,方法回收率均大于90%.研究表明,本方法专属性强,灵敏度高,线性关系良好,适用于这5种抗癫痫药物的血药浓度监测、个体化给药方案的制定、药物滥用监测以及药代动力学研究.
A new liquid chromatography-mass spectrometry method for the determination of carbamazepine,clonazepam,alprazolam,estazolam and phenytoin in human plasma has been developed by using diazepam as internal standard.Chromatographic separation was performed on a 3.5 μm Zorbax SB-C18 column(30 mm × 2.1 mm) with a mobile phase consisting of methanol and aqueous 25 mM ammonium acetate using gradient elution.A diethyl ether extraction method was used for the extraction of five anti-epilepsy drugs.Final extract was injected for analysis for LC-MS with MS2 mode.The method was validated within the concentration range of 50?5000 ng/mL for five anti-epilepsy drugs.The precision of the assay(RSD%) was less than 10% at all concentration levels within the tested range.The method recoveries for all samples were more than 90%.The results clearly indicate that the method is specific,sensitive and accurate,and suitable to study the pharmacokinetics,adjust the dosage for individual administration,and monitor the drug-concentration and drug abuse of the five anti-epilepsy drugs.
出处
《中国科学:化学》
CAS
CSCD
北大核心
2010年第6期762-767,共6页
SCIENTIA SINICA Chimica
基金
国家新药创新重大专项-武汉综合大平台(2009ZX09301)
国家自然科学基金(20775055
90817103&30973672)
教育部留学回国人员启动基金
中央高校基本科研业务专项基金
武汉大学珞珈特聘教授启动基金(306276216)资助
关键词
高效液相色谱
质谱
抗癫痫药
血药浓度
药物分析
high performance liquid chromatography
mass spectrometry
anti-epilepsy drugs
human plasma
drug analysis