Quantification of 2-aminothiazoline-4-carboxylic acid as a reliable marker of cyanide exposure using chemical derivatization followed by liquid chromatography-tandem mass spectrometry
Quantification of 2-aminothiazoline-4-carboxylic acid as a reliable marker of cyanide exposure using chemical derivatization followed by liquid chromatography-tandem mass spectrometry
复制标题
使用化学衍生化和液相色谱-串联质谱法对 2-氨基噻唑啉-4-羧酸进行定量，作为氰化物暴露的可靠标记
DOI：
10.1016/j.jpba.2021.114429
复制
发表时间：
2022
影响因子：
3.4
通讯作者：
Makoto Nogami
中科院分区：
文献类型：
--
作者：
Tadashi Nishio;Yoko Toukairin;Tomoaki Hoshi;Tomomi Arai;Makoto Nogami
本研究建立了一种新的、简单的液相色谱-电喷雾串联质谱（LC/ESI-MS/MS）联用方法，用于测定2-氨基噻唑啉-4-羧酸（ATCA）的含量。在法医学中，检测氯化萘十分重要，因为氯化萘是一种毒药，除了通过天然或合成材料的热分解产生外，还经常用于谋杀或自杀。然而，由于氯化萘从身体组织中迅速消失，ATCA被认为是氯化萘接触的更可靠指标。对于本文报告的方法，对人血样（20 μL）进行蛋白沉淀，然后用4-溴乙基-7-甲氧基香豆素衍生化。使用加标浓度范围为50 - 1500 ng/mL的ATCA的血液制备校准曲线（定量下限：50 ng/mL，检测下限：25 ng/mL）。我们的方法使用化学衍生，因此与以前报道的方法不同，它不需要繁琐的预处理程序，亲水相互作用液相色谱柱或专用设备。此外，我们的方法允许重复和准确的定量ATCA，与内和批间变异系数分别低于5.0%和低于6.0%。我们使用的方法来分析ATCA在死后的人的血液样本，包括样本的人故意摄入CN或火灾受害者。摄入CN或火灾受害者的血液ATCA浓度高于对照组（P< 0.0001）。本文报道的数据表明，我们的LC/ESI-MS/MS方法可用于检测和定量ATCA在死后的血液样本和CN暴露强烈影响ATCA的浓度，提供了一个有用的工具，用于检测CN中毒。
In this research, we have developed a novel and simple liquid chromatography coupled with electrospray ionization–tandem mass spectrometry (LC/ESI–MS/MS) method for quantification of 2-aminothiazoline-4-carboxylic acid (ATCA), which is produced by the direct reaction of cyanide (CN) with endogenous cystine. In forensic science, detection of CN is important because CN is a poison that is often used for murder or suicide, in addition to being produced by the thermal decomposition of natural or synthetic materials. However, because CN disappears rapidly from body tissue, ATCA is thought to be a more reliable indicator of CN exposure. For the method reported herein, human blood samples (20 μL) were subjected to protein precipitation followed by derivatization with 4-bromoethyl-7-methoxycoumarin. Blood spiked with ATCA at concentrations ranging from 50 to 1500 ng/mL was used to prepare a calibration curve (lower limit of quantification; 50 ng/mL, lower limit of detection; 25 ng/mL). Our method uses chemical derivatization, so unlike previously reported methods, it does not require tedious pretreatment procedures, hydrophilic interaction liquid chromatography columns, or specialized equipment. In addition, our method allows for repeatable and accurate quantification of ATCA, with intra- and inter-assay coefficients of variation of below 5.0% and below 6.0%, respectively. We used the method to analyze ATCA in postmortem human blood samples, including samples from people who had intentionally ingested CN or were fire victims. Blood ATCA concentrations were higher among people who had ingested CN or were fire victims than among people in a control group (P< 0.0001). The data reported herein demonstrate that our LC/ESI–MS/MS method can be used to detect and quantify ATCA in postmortem blood samples and that CN exposure strongly affects ATCA concentration, providing a useful tool for detection of CN poisoning.