用LC-MS/MS法测定血清中左乙拉西坦的浓度
Determination of levetiracetam concentration in serum by LC-MS/MS
安迪 1阎彦 1王娜 1张伟威 1张伟东1
作者信息
- 1. 秦皇岛市第一医院 药学部,河北 秦皇岛 066000
- 折叠
摘要
目的 建立测定人血清中左乙拉西坦浓度的液相色谱-串联质谱(LC-MS/MS)方法,并将该方法应用于癫痫患者左乙拉西坦治疗药物监测.方法 以左乙拉西坦-D6为内标,血清样品经蛋白沉淀后检测.Kinetex XB-C18(50.0 mm×3.0 mm,2.6 μm)为分析柱,以0.01％甲酸水溶液-甲醇为流动相,梯度洗脱,流速:0.4 mL·min-1,柱温:40℃,进样量:1 μL.电喷雾离子源,以正离子多离子反应监测扫描方式进行监测,定量分析离子对分别为m/z 171.1→154.2(左乙拉西坦)、m/z 177.1→160.1(左乙拉西坦-D6).对方法的专属性、线性范围和定量下限、准确度和精密度、稳定性进行考察,并将该方法应用于82例次癫痫患者左乙拉西坦治疗药物监测.结果 血清中左乙拉西坦浓度在1～100 μg·mL-1范围内线性关系良好,线性回归方程为y=0.573 7x+0.125 0(r=0.999 6).日内和日间精密度RSD均小于3.0％,回收率在93.67％～97.61％之间.82例次患者血药浓度范围为1.14～22.07 μg·mL-1.结论 本方法简便、快速、灵敏度高、专属性强、结果准确,可用于癫痫患者左乙拉西坦治疗药物监测.
Abstract
Objective To develop a method for determination of levetiracetam in human serum by LC-MS/MS,and it was applied to therapeutic drug monitoring in epilepsy patients.Methods Using levetiracetam-D6 as internal standard,the serum samples were tested after protein precipitation.The Kinetex XB-C18(50.0 mm x3.0 mm,2.6 μm)was used,the mobile phase consisted of methanol:0.01％formic acid water solution,gradient elution,the flow rate was 0.4 mL·min-1,and the column temperature was 40 ℃.The injection volume was 1 μL.Electron Spray Ionization source was applied and operated in multiple reaction monitoring mode.The quantitative analysis transitions were m/z 171.1→154.2(levetiracetam)and m/z 177.1→160.1(levetiracetam-D6).The specificity,lower limit of quantitation,linearity,precision,accuracy and stability were investigated.The method was applied to 82 cases of epilepsy patients for therapeutic drug monitoring.Results The calibration curve was y=0.573 7x+0.125 0(r=0.999 6),linear was within the range of 1-100 μg·mL-1 for levetiracetam in human serum.The relative standard deviation(RSD)of intra and inter precision were less than 3％.The recovery were between 93.67％-97.61％.The range of serum concentration of levetiracetam in 82 epilepsy patients was 1.14-22.07 μg·mL-1.Conclusions The method for determining levetiracetam concentration is simple,fast,sensitive,specific and accurate,which can be used for the therapeutic drug monitoring in epilepsy patients.
关键词
左乙拉西坦/液相色谱-串联质谱法/治疗药物监测Key words
levetiracetam/liquid chromatography tandem-mass spectrometry/therapeutic drug monitoring引用本文复制引用
基金项目
河北省博士后基金资助项目(B2021003046)
出版年
2024
国家科技期刊平台
NSTL
万方数据