Mirjam de Bruin-Hoegée , Alex Fidder , Tomas van Groningen , Marcel J. van der Schans , Daan Noort , Arian C. van Asten
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The fluoride-activated samples were analyzed by gas chromatography tandem mass spectrometry (GC–MS/MS) and LC-MS/MS. It was found that the CWA induced cholinesterase inhibition was remarkably stable in dried blood spots. Even after at least one month storage under ambient conditions, the same linear reduction was visible as function of nerve agent exposure. Additionally, nonapeptide adducts were identified by LC-MS/MS one month after exposure. Also, intact Novichok nerve agents and regenerated sarin were observed by GC–MS/MS. In addition to the stability of the sample, important benefits of the proposed method include the less invasive sample collection and safer and easier shipping and storage conditions. 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引用次数: 1
摘要
对生物医学样本的分析对于调查指称的化学战剂接触很重要。本研究旨在利用干血点进行有机磷中毒的便携式检测和实验室验证。将血液与Novichok a -230、a -232、a -234和沙林体外孵育后，在蛋白储存卡上标记25µL和50µL的体积。随后，提取干燥斑点，用移动胆碱酯酶检测试剂盒进行分析。另外，用胃蛋白酶分离提取丁基胆碱酯酶(BChE)，用液相色谱-串联质谱(LC-MS/MS)分析。采用气相色谱-串联质谱(GC-MS /MS)和LC-MS/MS对氟化物活化样品进行分析。结果发现，CWA诱导的胆碱酯酶抑制在干血斑中具有显著的稳定性。即使在环境条件下储存至少一个月后，神经毒剂暴露后，同样的线性减少也是可见的。此外，暴露1个月后用LC-MS/MS鉴定了非肽加合物。同时用GC-MS /MS观察完整的诺维乔克神经毒剂和再生沙林。除了样品的稳定性外，该方法的重要优点还包括较少的侵入性样品采集以及更安全，更容易的运输和储存条件。总之，本研究表明，使用现场检测和最先进的实验室分析干血斑，以明确验证神经毒剂暴露的可行性。
On-site detection and laboratory verification of the presence of nerve agent biomarkers using dried blood spots
The analysis of biomedical samples is important for the investigation of the alleged exposure to chemical warfare agents. The present study aims to use dried blood spots for portable detection and laboratory verification of organophosphate poisoning. After in-vitro incubation of blood with Novichok A-230, A-232 and A-234 and sarin, a volume of 25 and 50 µL was spotted on a protein saver card. Subsequently, the dried spots were extracted and analyzed by a mobile cholinesterase test kit. In addition, butyrylcholinesterase (BChE) was isolated and digested by pepsin followed by analysis with liquid chromatography tandem mass spectrometry (LC-MS/MS). The fluoride-activated samples were analyzed by gas chromatography tandem mass spectrometry (GC–MS/MS) and LC-MS/MS. It was found that the CWA induced cholinesterase inhibition was remarkably stable in dried blood spots. Even after at least one month storage under ambient conditions, the same linear reduction was visible as function of nerve agent exposure. Additionally, nonapeptide adducts were identified by LC-MS/MS one month after exposure. Also, intact Novichok nerve agents and regenerated sarin were observed by GC–MS/MS. In addition to the stability of the sample, important benefits of the proposed method include the less invasive sample collection and safer and easier shipping and storage conditions. In conclusion, this study shows the feasibility of using on-site detection and state-of-the-art laboratory analysis of dried blood spots for unambiguous verification of nerve agent exposure.
期刊介绍：
Forensic Chemistry publishes high quality manuscripts focusing on the theory, research and application of any chemical science to forensic analysis. The scope of the journal includes fundamental advancements that result in a better understanding of the evidentiary significance derived from the physical and chemical analysis of materials. The scope of Forensic Chemistry will also include the application and or development of any molecular and atomic spectrochemical technique, electrochemical techniques, sensors, surface characterization techniques, mass spectrometry, nuclear magnetic resonance, chemometrics and statistics, and separation sciences (e.g. chromatography) that provide insight into the forensic analysis of materials. Evidential topics of interest to the journal include, but are not limited to, fingerprint analysis, drug analysis, ignitable liquid residue analysis, explosives detection and analysis, the characterization and comparison of trace evidence (glass, fibers, paints and polymers, tapes, soils and other materials), ink and paper analysis, gunshot residue analysis, synthetic pathways for drugs, toxicology and the analysis and chemistry associated with the components of fingermarks. The journal is particularly interested in receiving manuscripts that report advances in the forensic interpretation of chemical evidence. Technology Readiness Level: When submitting an article to Forensic Chemistry, all authors will be asked to self-assign a Technology Readiness Level (TRL) to their article. The purpose of the TRL system is to help readers understand the level of maturity of an idea or method, to help track the evolution of readiness of a given technique or method, and to help filter published articles by the expected ease of implementation in an operation setting within a crime lab.
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