Lee Junhui, Park Jiwon, Go Ahra, Moon Heesung, Kim Sujin, Jung Sohee, Jeong Wonjoon, Chung Heesun
Graduate School of Analytical Science and Technology, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon, Korea.
Department of Emergency Medicine, Chungnam National University Hospital, Daejeon, Korea.
J Anal Toxicol. 2018 Nov 1;42(9):617-624. doi: 10.1093/jat/bky032.
To intoxicated patients in the emergency room, toxicological analysis can be considerably helpful for identifying the involved toxicants. In order to develop a urine multi-drug screening (UmDS) method, gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-tandem mass spectrometry (LC-MS-MS) were used to determine targeted and unknown toxicants in urine. A GC-MS method in scan mode was validated for selectivity, limit of detection (LOD) and recovery. An LC-MS-MS multiple reaction monitoring (MRM) method was validated for lower LOD, recovery and matrix effect. The results of the screening analysis were compared with patient medical records to check the reliability of the screen. Urine samples collected from an emergency room were extracted through a combination of salting-out assisted liquid-liquid extraction (SALLE) and hybrid protein precipitation/solid phase extraction (hybrid PPT/SPE) plates and examined by GC-MS and LC-MS-MS. GC-MS analysis was performed as unknown drug screen and LC-MS-MS analysis was conducted as targeted drug screen. After analysis by GC-MS, a library search was conducted using an in-house library established with the automated mass spectral deconvolution and identification system (AMDISTM). LC-MS-MS used Cliquid®2.0 software for data processing and acquisition in MRM mode. An UmDS method by GC-MS and LC-MS-MS was developed by using a SALLE-hybrid PPT/SPE and in-house library. The results of UmDS by GC-MS and LC-MS-MS showed that toxicants could be identified from 185 emergency room patient samples containing unknown toxicants. Zolpidem, acetaminophen and citalopram were the most frequently encountered drugs in emergency room patients. The UmDS analysis developed in this study can be used effectively to detect toxic substances in a short time. Hence, it could be utilized in clinical and forensic toxicology practices.
对于急诊室中的中毒患者，毒理学分析在识别所涉及的毒物方面可能会有很大帮助。为了开发一种尿液多药物筛查（UmDS）方法，采用气相色谱 - 质谱联用（GC - MS）和液相色谱 - 串联质谱联用（LC - MS - MS）来测定尿液中的目标毒物和未知毒物。对扫描模式下的GC - MS方法进行了选择性、检测限（LOD）和回收率的验证。对LC - MS - MS多反应监测（MRM）方法进行了更低LOD、回收率和基质效应的验证。将筛查分析结果与患者病历进行比较，以检查筛查的可靠性。从急诊室收集的尿液样本通过盐析辅助液 - 液萃取（SALLE）和混合蛋白沉淀/固相萃取（混合PPT/SPE）板相结合的方法进行提取，并通过GC - MS和LC - MS - MS进行检测。GC - MS分析作为未知药物筛查进行，LC - MS - MS分析作为目标药物筛查进行。通过GC - MS分析后，使用通过自动质谱解卷积和鉴定系统（AMDISTM）建立的内部数据库进行库检索。LC - MS - MS使用Cliquid®2.0软件在MRM模式下进行数据处理和采集。通过使用SALLE - 混合PPT/SPE和内部数据库开发了一种基于GC - MS和LC - MS - MS的UmDS方法。GC - MS和LC - MS - MS的UmDS结果表明，从185份含有未知毒物的急诊室患者样本中可以鉴定出毒物。唑吡坦、对乙酰氨基酚和西酞普兰是急诊室患者中最常遇到的药物。本研究中开发的UmDS分析可有效地在短时间内检测有毒物质。因此，它可用于临床和法医毒理学实践。
