Drugs of abuse screening in urine as part of a metabolite-based LC-MSn screening concept
Drugs of abuse screening in urine as part of a metabolite-based LC-MSn screening concept
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DOI：
10.1007/s00216-011-5032-1
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发表时间：
2011-07-01
影响因子：
4.3
通讯作者：
Maurer, Hans H.
中科院分区：
文献类型：
--
作者：
Wissenbach, Dirk K.;Meyer, Markus R.;Maurer, Hans H.
今天，免疫分析和几种层析方法被用于临床和法医毒理学以及兴奋剂检查中的药物筛选。为了进一步证明作者提出的新的基于代谢物的液质联用(LC-MSN)筛选概念，研究了利用该筛选方法对滥用药物及其代谢物的检测能力。如以前报道的，使用LXQ线性离子陷阱，正模式电喷雾电离和全扫描信息依赖获取，建立了相应的参考库，获得了MS2和MS3宽带光谱。除了在甲醇溶液中记录的母体药物谱外，在给药后的大鼠尿液中蛋白质沉淀后的代谢物谱被鉴定并添加到文库中。现在包括900多种母体化合物的数据，包括87种滥用药物，以及2,300多种代谢物和人工制品，其中包括436种滥用药物。用添加的人尿测定了选定滥用药物的回收率、过程效率、基质效应和检测限，结果数据是可以接受的。使用ToxID和SmileMS两种自动数据评估工具，通过蛋白质沉淀和LC分离，可以在吸毒者的尿样中确定54种被研究滥用药物的摄入量。涵盖以下药物类别：兴奋剂、设计药物、致幻剂、(合成)大麻类、阿片类药物和选定的苯二氮卓类药物。所提出的LC-MSN方法是对作者实验室中成熟的气相色谱-质谱分析方法的补充。
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-MSn) 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 MS2 and MS3 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-MSn method complements the well-established gas chromatography-mass spectroscopy procedure in the authors' laboratory.