高效液相色谱-三重四极杆复合线性离子阱质谱法检测血液中8种苯二氮卓类药物  

Determination of Eight Benzodiazepines in Blood by High-performance Liquid Chromatography-Triple Quadrupole Linear Ion Trap Mass Spectrometry

作　　者：胡骏杰 刘飞 马文俊 上官国强 HU Jun-jie;LIU Fei;MA Wen-jun;SHANGGUAN Guo-qiang(Judicial Expertise Center,Jining Medical University,Jining 272067,China;College of Forensic Medicine and Laboratory Medicine,Jining Medical University,Jining 272067,China;State Key Laboratory of Analytical Chemistry for Life Science,School of Chemistry and Chemical Engineering,Nanjing University,Nanjing 210023,China)

机构地区：[1]济宁医学院司法鉴定中心,山东济宁272067 [2]济宁医学院法医学与医学检验学院,山东济宁272067 [3]南京大学化学化工学院,生命分析化学国家重点实验室,江苏南京210023

出　　处：《分析测试学报》2021年第4期577-582,共6页Journal of Instrumental Analysis

基　　金：国家自然科学基金项目(21904049);国家级大学生创新训练计划项目(201910443005);济宁医学院大学生创新训练计划项目(cx2019061);山东省高等学校科技计划项目(J18KB047);济宁医学院教师扶持基金项目(JYFC2018FY005)。

摘　　要：建立了血液样本中8种苯二氮卓类药物的高效液相色谱-三重四极杆复合线性离子阱质谱(QTRAP HPLC-MS/MS)检测方法。血液样本经乙腈沉淀蛋白法处理,离心取上清液,过滤后采用分段多反应监测结合信息依赖性采集与增强离子扫描(sMRM-IDA-EPI)模式分析,结合EPI二级谱库检索确证可疑检出物,以sMRM数据采用外标法定量检测。8种苯二氮卓类药物在0.5~50 ng/mL范围内线性关系良好(r>0.998);检出限为0.01~0.10 ng/mL,定量下限为0.10~0.25 ng/mL;化合物在1.0、5.0、20 ng/mL 3个加标水平下的回收率为79.3%~112%,基质效应为79.8%~97.2%,相对标准偏差为4.3%~11%。该方法操作简便,结果准确,适用于中毒患者病情的快速确诊与评估,可为医疗急救与中毒检测提供技术支持。Benzodiazepines are one of the most frequently prescribed drugs with a broad range of therapeutic effects,including sedative hypnotic,anxiolytic,muscle relexation and anticonvulsant.However,the potential possibility for addiction and abuse in both clinical and forensic cases greatly increased due to the high consumption of benzodiazepines all over the world.For this reason,it is essential to develop a rapid and accurate approach for the determination of benzodiazepines.In this paper,a method was developed for the detection of eight representative benzodiazepines,including diazepam,nitrazepam,clonazepam,flunitrazepam,lorazepam,alprazolam,estazolam,and midazolam in blood samples by high-performance liquid chromatography-triple quadrupole linear ion trap mass spectrometry(QTRAP HPLC-MS/MS).Brief steps for the method construction are described as follows.Firstly,the MS/MS library of target analytes with three collision energies were established for the searching and fitting of suspicious detected compounds.Secondly,the instrument conditions were optimized,with Phenomenex Kinetex?Biphenyl(100 mm×3.0 mm,2.6μm)as the column for separation,and 5 mmol/L ammonium acetate containing 0.1%formic acid and methanol as mobile phases for gradient elution.Finally,different pretreatment methods for blood samples,including liquid-liquid extraction using organic solvent,and protein precipitation using methanol or acetonitrile were compared,and the method of acetonitrile protein precipitation was selected owing to the convenience in handling and its relatively high recoveries for target analytes.With the optimized parameter and condition,the blood samples were firstly processed by the acetonitrile protein precipitation method,then centrifuged to obtain the supernatant,and finally filtered for analysis.Scheduled multiple reaction monitoring combined with information-dependent acquisition and enhanced product ion(sMRM-IDA-EPI)scanning mode with electrospray ionization(ESI)under the positive condition was applied to data acquisition,wi

关 键 词：高效液相色谱-三重四极杆复合线性离子阱质谱 血液 苯二氮卓类药物 中毒检测 

分 类 号：O657.63[理学—分析化学]