超高效液相色谱法分析人血清中拉莫三嗪、奥卡西平及其代谢物浓度  

Analysis of the concentrations of lamotrigine,oxcarbazepine and its active metabolite in human serum by UPLC method

作　　者：董维冲 郭家良[3] 李亚前 刘姣 李德强[1] 蒋晔[2] 张志清[1] DONG Wei-chong;GUO Jia-liang;LI Ya-qian;LIU Jiao;LI De-qiang;JIANG Ye;ZHANG Zhi-qing(Department of Pharmacy,The Second Hospital of Hebei Medical University,Shijiazhuang 050051,Hebei Province,China;School of Pharmacy,Hebei Medical University,Shijiazhuang 050017,Hebei Province,China;Department of Orthopedics,The Third Hospital of Hebei Medical University,Shijiazhuang 050000,Hebei Province,China)

机构地区：[1]河北医科大学第二医院药学部,河北石家庄050051 [2]河北医科大学药学院,河北石家庄050017 [3]河北医科大学第三医院骨科,河北石家庄050000

出　　处：《中国临床药理学杂志》2022年第5期453-456,共4页The Chinese Journal of Clinical Pharmacology

基　　金：河北省科技厅科技计划基金资助项目(19277728D);河北省卫健委医学科学研究课题基金资助项目(20200897)。

摘　　要：目的建立一种超高效液相色谱法(UPLC),同时分析人血清中拉莫三嗪(LTG)、奥卡西平(OXC)及其代谢物10,11-二氢-10-羟基卡马西平(MHD)浓度,并用于本院治疗药物监测。方法血清样本经乙醚萃取,采用Waters UPLC BEH C;柱(50.0 mm×2.1 mm, 1.7μm),流动相为乙腈-磷酸缓冲盐(pH 4.5)=26∶74;流速:0.2 mL·min^(-1);柱温:30℃;检测波长:220 nm,进样量:2μL,内标为非那西丁,考察该方法的专属性、标准曲线、精密度、准确度、稳定性,收集临床癫痫患者血清样本进行方法验证。结果血清中LTG、OXC和MHD分离良好,不受血清中内源性物质干扰,色谱分析时间仅需5 min,血清中LTG和OXC在0.25~25.00μg·mL;和MHD在0.50~50.00μg·mL;范围内线性关系均良好,方法回收率为88.37%~105.00%,LTG、MHD和OXC的绝对回收率分别可达78.45%,62.50%和75.76%以上,内标的提取回收率为61.41%。批内、批间RSD均不大于7.0%,室温放置16 h、冻融循环3次和冰冻30 d的稳定性良好。所建方法在本院临床采用LTG治疗癫痫的患者10例和服用OXC治疗癫痫患者7例中进行验证。结论所建方法简便准确,提高了分析效率,适宜于LTG、OXC和MHD的临床常规血药浓度监测,并成功用于本院治疗药物监测。Objective To establish an ultra-high performance liquid chromatography (UPLC) method for the simultaneous analysis of the concentration of lamotrigine (LTG),oxcarbazepine (OXC) and its active metabolite,10,11-dihydro10-hydroxycarbamazepine (MHD)in human serum for clinical therapeutic drug monitoring.Methods The serum samples were prepared by liquid-liquid extraction with diethyl ether.Waters UPLC BEH C;column (50.0 mm×2.1 mm,1.7μm)was used.The mobile phase consisted of acetonitrile and phosphate buffer(pH 4.5)(26∶74) at the flow rate of 0.2 m L·min^(-1).The column temperature was maintained at 30℃.The detected wavelength was 220 nm.The injection volume was 2μL.The internal label was phenacetin.The selectivity,linearity,precision,accuracy and stability of the method were investigated.Serum samples from clinical epilepsy patients were collected for method validation.Results LTG,OXC and MHD in serum were separated well,and were not disturbed by endogenous substances in serum.The chromatographic analytical time was only 5 min.The good linear relationship were obtained between concentration of LTG and OXC both from 0.25-25.00μg·m L;,and MHD form 0.50-50.00μg·m L;.The method recovery rates were 88.37%-105.00%.The absolute recoveries of LTG,MHD and OXC were 78.45%,62.50%and 75.76%,respectively.The extraction recoveries of internal standard were 61.41%.The intra-day and inter-day precision (RSD) were all less than 7.0%.The stability was good after being placed at room temperature for 16 h,freeze-thaw cycles for 3 times and frozen for 30 d.The established method was validated in 10 patients with epilepsy treated with LTG and 7 patients with OXC in our hospital.Conclusion The present method is simple,accurate and could improve the analysis efficiency which is suitable for analysis of the concentrations of lamotrigine,oxcarbazepine and its active metabolite in human serum.It was successfully used in the therapeutic drug monitoring in our hospital.

关 键 词：拉莫三嗪 奥卡西平 10 11-二氢-10-羟基卡马西平 超高效液相色谱 血药浓度 治疗药物监测 

分 类 号：R969.1[医药卫生—药理学]