Knuth Marianne, Temme Oliver, Daldrup Thomas, Pawlik Evelyn
Institute of Legal Medicine, University Hospital Duesseldorf, Moorenstraße 5, 40225 Duesseldorf, Germany.
Institute of Legal Medicine, University Hospital Duesseldorf, Moorenstraße 5, 40225 Duesseldorf, Germany.
Forensic Sci Int. 2018 Apr;285:86-92. doi: 10.1016/j.forsciint.2018.02.001. Epub 2018 Feb 10.
For different reasons, street cocaine is often diluted with pharmacologically active substances, the so-called adulterants such as levamisole or hydroxyzine. A controversial debate exists currently on the uptake of adulterants from cocaine preparations and drug-related death. Previous research convincingly argues that serious adverse side effects that affect the central nervous and cardiovascular systems can be a consequence of adulterated cocaine.
Having identified the presence of adulterants in lung tissue and blood, the concentrations of these substances in brain, an important target location, was of interest. This provides an opportunity to assess their role in cases of drug-related deaths.
We developed and validated a method for the analysis of cocaine, two cocaine metabolites and six adulterants, which can typically be found in cocaine preparations, and one adulterant metabolite in brain tissue by gas chromatography-mass spectrometry (GC-MS). Ten brain samples which were tested positive for cocaine were analyzed. The homogenized brain tissue was embedded into drying paper for protein precipitation. During a subsequent solid-phase extraction (SPE), the eluate and one of the wash fractions were collected. After derivatization with N-Methyl-N-(trimethylsilyl)trifluoroacetamide (MSTFA) in pyridine and isooctane, the extracts were analyzed by GC-MS.
The method was fully validated for cocaine (COC), benzoylecgonine (BZE), ecgonine methyl ester (EME), diltiazem (DIL), hydroxyzine (HYD), and levamisole (LEV) and partly validated for cetirizine (CET), lidocaine (LID), phenacetin (PHE), and procaine (PRO) in brain material. By analyzing post-mortem brain tissue of ten cocaine users, LEV, LID, and HYD as well as PHE were identified in contrast to DIL, PRO, and the HYD metabolite CET. HYD and LEV were found in moderate to high concentrations in some cases. Therefore, it cannot be excluded that they have caused adverse side effects.
Because adulterants can potentially affect the central nervous and cardiac systems, it is likely that they enhance COC toxicity.
由于各种原因，街头可卡因常常被与药理活性物质混合稀释，这些物质即所谓的掺杂物，如左旋咪唑或羟嗪。目前关于从可卡因制剂中摄取掺杂物与药物相关死亡存在争议性辩论。先前的研究令人信服地表明，掺假可卡因可能导致影响中枢神经和心血管系统的严重不良副作用。
在确定肺组织和血液中存在掺杂物后，重要目标部位大脑中这些物质的浓度成为研究关注点。这为评估它们在药物相关死亡案例中的作用提供了契机。
我们开发并验证了一种通过气相色谱 - 质谱联用（GC - MS）分析可卡因、两种可卡因代谢物以及六种通常在可卡因制剂中能找到的掺杂物和一种掺杂物代谢物在脑组织中的方法。对十个可卡因检测呈阳性的脑样本进行了分析。将匀浆后的脑组织嵌入干燥纸中进行蛋白质沉淀。在随后的固相萃取（SPE）过程中，收集洗脱液和一个洗涤馏分。在用吡啶和异辛烷中的N - 甲基 - N - （三甲基硅基）三氟乙酰胺（MSTFA）进行衍生化后，通过GC - MS对提取物进行分析。
该方法在脑组织中对可卡因（COC）、苯甲酰爱康宁（BZE）、芽子碱甲酯（EME）、地尔硫䓬（DIL）、羟嗪（HYD）和左旋咪唑（LEV）进行了全面验证，对西替利嗪（CET）、利多卡因（LID）、非那西丁（PHE）和普鲁卡因（PRO）进行了部分验证。通过分析十名可卡因使用者的死后脑组织，与地尔硫䓬、普鲁卡因和羟嗪代谢物西替利嗪不同，发现了左旋咪唑、利多卡因和羟嗪以及非那西丁。在某些案例中发现羟嗪和左旋咪唑的浓度处于中到高水平。因此，不能排除它们造成了不良副作用。
由于掺杂物可能影响中枢神经和心脏系统，它们很可能增强了可卡因的毒性。
