Department of Experimental and Clinical Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, Saarland University, Homburg (Saar), Germany.
Anal Bioanal Chem. 2011 Jul;400(10):3481-9. doi: 10.1007/s00216-011-5032-1. Epub 2011 May 1.
Today, immunoassays and several chromatographic methods are in use for drug screening in clinical and forensic toxicology and in doping control. For further proof of the authors' new metabolite-based liquid chromatography-mass spectrometry (LC-MS(n)) screening concept, the detectability of drugs of abuse and their metabolites using this screening approach was studied. As previously reported, the corresponding reference library was built up with MS(2) and MS(3) wideband spectra using a LXQ linear ion trap with electrospray ionization in the positive mode and full scan information-dependent acquisition. In addition to the parent drug spectra recorded in methanolic solution, metabolite spectra were identified after protein precipitation of urine from rats after administration of the corresponding drugs and added to the library. This consists now of data of over 900 parent compounds, including 87 drugs of abuse, and of over 2,300 metabolites and artifacts, among them 436 of drugs of abuse. Recovery, process efficiency, matrix effects, and limits of detection for selected drugs of abuse were determined using spiked human urine, and the resulting data have been acceptable. Using two automatic data evaluation tools (ToxID and SmileMS), the intake of 54 of the studied drugs of abuse could be confirmed in urine samples of drug users after protein precipitation and LC separation. The following drugs classes were covered: stimulants, designer drugs, hallucinogens, (synthetic) cannabinoids, opioids, and selected benzodiazepines. The presented LC-MS(n) method complements the well-established gas chromatography-mass spectroscopy procedure in the authors' laboratory.
目前，免疫分析和几种色谱方法被用于临床和法医毒物学以及兴奋剂控制中的药物筛选。为了进一步证明作者基于新代谢物的液相色谱-质谱（LC-MS(n)）筛选概念的有效性，研究了该筛选方法对滥用药物及其代谢物的检测能力。如前所述，使用具有电喷雾电离正模式和全扫描信息相关采集的 LXQ 线性离子阱，通过 MS(2)和 MS(3)宽带光谱构建了相应的参考库。除了在甲醇溶液中记录的母体药物光谱外，还在给予相应药物后对大鼠尿液进行蛋白沉淀，并将代谢物光谱鉴定后添加到库中。该库现在包含超过 900 种母体化合物的数据，包括 87 种滥用药物，以及超过 2300 种代谢物和人工产物，其中包括 436 种滥用药物。使用加标人尿确定了选定的滥用药物的回收率、过程效率、基质效应和检测限，并获得了可接受的数据。使用两个自动数据评估工具（ToxID 和 SmileMS），在对滥用药物进行蛋白沉淀和 LC 分离后，可在药物使用者的尿液样本中确认 54 种研究药物的摄入情况。涵盖的药物类别包括兴奋剂、设计药物、迷幻剂、（合成）大麻素、阿片类药物和选定的苯二氮䓬类药物。所提出的 LC-MS(n)方法补充了作者实验室中成熟的气相色谱-质谱程序。
