Rużycka Monika, Giebułtowicz Joanna, Fudalej Marcin, Krajewski Paweł, Wroczyński Piotr
Bioanalysis and Drugs Analysis Department, Faculty of Pharmacy, Medical University of Warsaw , 1 Banacha Street, 02-097 Warsaw, Poland.
Forensic Medicine Department, Medical University of Warsaw , 1 Oczki Street, 02-007 Warsaw, Poland.
Chem Res Toxicol. 2017 Feb 20;30(2):516-523. doi: 10.1021/acs.chemrestox.6b00219. Epub 2017 Feb 7.
Cyanides are infamous for their highly poisonous properties. Accidental cyanide poisoning occurs frequently, but occasionally, intentional poisonings also occur. Inhalation of fumes generated by fire may also cause cyanide poisoning. There are many limitations in direct analysis of cyanide. 2-Aminothiazoline-4-carboxylic acid (ATCA), a cyanide metabolite, seems to be the only surrogate that is being used in the detection of cyanide because of its stability and its cyanide-dependent quality in a biological matrix. Unfortunately, toxicokinetic studies on diverse animal models suggest significant interspecies differences; therefore, the attempt to extrapolate animal models to human models may be unsuccessful. The aim of the present study was to evaluate the use of ATCA as a forensic marker of cyanide exposure. For this purpose, post-mortem materials (blood and organs) from fire victims (n = 32) and cyanide-poisoned persons (n = 3) were collected. The distribution of ATCA in organs and its thermal stability were evaluated. The variability of cyanides in a putrid sample and in the context of their long-term and higher temperature stability was established. The presence of ATCA was detected by using an LC-MS/MS method and that of cyanide was detected spectrofluorimetrically. This is the first report on the endogenous ATCA concentrations and the determination of ATCA distribution in tissues of fire victims and cyanide-poisoned persons. It was found that blood and heart had the highest ATCA concentrations. ATCA was observed to be thermally stable even at 90 °C. Even though the cyanide concentration was not elevated in putrid samples, it was unstable during long-term storage and at higher temperature, as expected. The relationship between ATCA and cyanides was also observed. Higher ATCA concentrations were related to increased levels of cyanide in blood and organs (less prominent). ATCA seems to be a reliable forensic marker of exposure to lethal doses of cyanide.
氰化物因其剧毒特性而声名狼藉。意外氰化物中毒屡见不鲜，但偶尔也会发生故意中毒事件。吸入火灾产生的烟雾也可能导致氰化物中毒。氰化物的直接分析存在诸多局限性。2-氨基噻唑啉-4-羧酸（ATCA）作为一种氰化物代谢产物，因其稳定性以及在生物基质中依赖氰化物的特性，似乎是检测氰化物时唯一被使用的替代物。不幸的是，对多种动物模型的毒代动力学研究表明存在显著的种间差异；因此，将动物模型外推至人类模型的尝试可能并不成功。本研究的目的是评估ATCA作为氰化物暴露法医标志物的用途。为此，收集了火灾受害者（n = 32）和氰化物中毒者（n = 3）的死后材料（血液和器官）。评估了ATCA在器官中的分布及其热稳定性。确定了腐败样本中氰化物的变异性以及它们在长期和高温下的稳定性情况。采用液相色谱-串联质谱法检测ATCA的存在，并用荧光分光光度法检测氰化物的存在。这是关于火灾受害者和氰化物中毒者组织中内源性ATCA浓度及ATCA分布测定的首份报告。研究发现血液和心脏中的ATCA浓度最高。即使在90℃时，ATCA仍具有热稳定性。尽管腐败样本中的氰化物浓度未升高，但正如预期的那样，它在长期储存和高温下不稳定。还观察到了ATCA与氰化物之间的关系。较高的ATCA浓度与血液和器官中氰化物水平的升高相关（不太显著）。ATCA似乎是暴露于致死剂量氰化物的可靠法医标志物。
