用HPLC-MS/MS法测定儿童微量血浆中多种治疗性药物的浓度  

Determination of multifarious drugs in trace plasma of children by HPLC-MS/MS

作　　者：秦亚彬 张古英[1] 孙玉林 赵德运[1] QIN Ya-bin;ZHANG Gu-ying;SUN Yu-lin;ZHAO De-yun(Department of Pharmacy,Children's Hospital of Hebei Province,Shijiazhuang 050031,Hebei Province,China)

机构地区：[1]河北省儿童医院药学部,河北石家庄050031

出　　处：《中国临床药理学杂志》2023年第23期3469-3474,共6页The Chinese Journal of Clinical Pharmacology

基　　金：河北省卫健委医学科学研究课题基金资助项目(20190795)。

摘　　要：目的 建立血浆中多种治疗性药物浓度测定的高效液相色谱串联质谱法,并用于儿童患者治疗药物监测。方法 取血浆样本10μL,经甲醇沉淀蛋白,色谱柱:Phenomenex Kinetex EVO C_(18)(50.0 mm×2.1 mm, 2.6μm)色谱柱分离,流动相:水含1.0×10^(-5)mmol·L^(-1)甲酸-甲醇,梯度洗脱,流速:0.45 mL·min^(-1),柱温:45℃。电喷雾电离,正负离子切换,动态多反应监测扫描。结果 甲氨蝶呤线性范围为31.25~1 000.00 ng·mL^(-1)、丙戊酸线性范围为6.25~200.00μg·mL^(-1)、左乙拉西坦和10,11-二氢-10-羟基卡马西平线性范围均为1.56~50.00μg·mL^(-1)、拉莫三嗪和卡马西平线性范围均为0.78~25.00μg·mL^(-1),各待测物的线性关系良好(均R^(2)>0.99)。该方法的专属性、准确度、精密度、基质效应和稳定性均符合要求。本方法应用于治疗药物监测,已完成498例患儿样本检测。结论 本方法操作简便、快速,灵敏度良好,适用于儿童患者临床治疗药物监测。Objective To develop a high performance liquid chromatography-tandem mass spectrometry method for simultaneous determination of multifarious drugs in human plasma for therapeutic drug monitoring in children.Methods The proteins in 10μL plasma samples were precipitated by methanol.The chromatographic conditions were as following:chromatographic column:Phenomenex Kinetex EVO C_(18)column(50×2.1 mm,2.6μm),mobile phase:water(1.0×10^(-5)formic acid)-methanol,flow rate:0.45 mL·min^(-1),The column temperature:45℃.The electrospray ionization source was used and the mass detection was performed using dynamic multiple reaction monitoring mode with ionization polarity switching.Results In plasma samples,methotrexate(linear range 31.25-1000.00 ng·mL^(-1)),levetiracetam and 10,11-dihydro-10-hydroxycarbazepine(linear range 1.56-50.00μg·mL^(-1)),lamotrigine and carbamazepine(linear range 0.78-25.00μg·mL^(-1)),showed good linear relationships under this method(all R^(2)>0.99).The specificity,precision and accuracy values for intra-and inter-assays,matrix effect,stability all met the requirements.This method was applied to the therapeutic drug monitoring in 498 pediatric patients.Conclusion The method is simple,sensitive,rapid and suitable for children therapeutic drug monitoring.

关 键 词：甲氨蝶呤 抗癫痫药物 高效液相色谱串联质谱法 治疗药物监测 儿童 

分 类 号：R971[医药卫生—药品]