| 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 |
| 点此下载全文 |
|
| 基金项目: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) |
|
| 中文摘要: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。 |
| 中文关键词: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 |
| |
| Determination of Eight Benzodiazepines in Blood by High-performance Liquid Chromatography-Triple Quadrupole Linear Ion Trap Mass Spectrometry |
|
|
| Abstract: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×30 mm,26 μm) as the column for separation,and 5 mmol/L ammonium acetate containing 01% 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,with which the suspicious detected compounds could be confirmed by EPI library searching,and quantitative analysis could be carried out with external standard method according to sMRM data.Eight benzodiazepines showed good linear relationships in the concentration range of 05-50 ng/mL with their correlation coefficients(r) larger than 0998.The limits of detection(LOD,S/N≥3) for eight benzodiazepines were in the range of 001-010 ng/mL,while the limits of quantitation(LOQ,S/N≥10) were 010-025 ng/mL.Recoveries for eight compounds at three spiked levels of 10,50 and 20 ng/mL ranged from 793% to 112%,with matrix effects of 798%-972% and relative standard deviations of 43%-11%.Owing to the simple steps of the experiment,the entire process could be completed with reliable and accurate results.The established method was successfully validated by its application in the benzodiazepines screening of a blood sample from the local emergency department.Three compounds of diazepam,alprazolam and midazolam were detected and confirmed,with their concentrations of 3057,651 and 6869 ng/mL,respectively.This method is suitable for rapid diagnosis and condition evaluation of poisoning patients,and provides a technical support for medical emergency and poisoning detection. |
| Key Words:high-performance liquid chromatography-triple quadrupole linear ion trap mass spectrometry blood benzodiazepines poisoning detection |
| 引用本文：胡骏杰,刘飞,马文俊,上官国强.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[J].分析测试学报,2021,40(4):577-582. |
| 摘要点击次数: 1644 |
| 全文下载次数: 793 |
| 查看全文 下载PDF阅读器 |
|
|
|
|
|
