Deploying Validated Mass Spectrometry for Frontline Detection and Treatment of Human Poisoning by Long-Acting Anticoagulant Rodenticides.

IF 3.7 3区 医学 Q2 CHEMISTRY, MEDICINAL Chemical Research in Toxicology Pub Date : 2024-10-29 DOI:10.1021/acs.chemrestox.4c00344
Richard B van Breemen, Bianca Flores, Israel Rubinstein, Douglas L Feinstein
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Abstract

Derived from the same natural anticoagulant as warfarin (dicoumarol), long-acting anticoagulant rodenticides (LAARs) or superwarfarins have much longer half-lives in human blood than warfarin (weeks instead of hours) and are more potent inhibitors of the same enzyme, vitamin K epoxide reductase component 1. While used effectively worldwide as rodenticides, LAARs can elicit severe, protracted, life-threatening coagulopathy in humans at blood concentrations >10 ng/mL leading to numerous accidental and intentional poisonings annually. To facilitate timely identification and quantitative analysis of LAARs in patients presenting unexplained severe, protracted, life-threatening coagulopathy, several analytical methods have been developed, all of which are based on electrospray liquid chromatography-mass spectrometry (LC-MS). In this perspective, we evaluated and compared these LC-MS methods in terms of validation, simultaneous detection of multiple LAARs, measurement of individual stereoisomers, and clinical applications.

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将经过验证的质谱法用于长效抗凝灭鼠剂人类中毒的一线检测和治疗。
长效抗凝血灭鼠剂(LAARs)或超级矮壮素从与华法林(双香豆素)相同的天然抗凝剂中提取,在人体血液中的半衰期比华法林长得多(数周而不是数小时),并且是同一种酶(维生素 K 环氧化物还原酶成分 1)的更强效抑制剂。虽然 LAARs 在全球范围内被有效地用作杀鼠剂,但当其在人体内的血药浓度大于 10 纳克/毫升时,就会引发严重、持久、危及生命的凝血病,导致每年发生多起意外和故意中毒事件。为了便于及时鉴定和定量分析不明原因的严重、持久、危及生命的凝血病患者体内的 LAARs,目前已开发出多种分析方法,所有这些方法都基于电喷雾液相色谱-质谱法(LC-MS)。在本研究中,我们从验证、多种 LAARs 的同时检测、单个立体异构体的测量和临床应用等方面对这些 LC-MS 方法进行了评估和比较。
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来源期刊
CiteScore
7.90
自引率
7.30%
发文量
215
审稿时长
3.5 months
期刊介绍: Chemical Research in Toxicology publishes Articles, Rapid Reports, Chemical Profiles, Reviews, Perspectives, Letters to the Editor, and ToxWatch on a wide range of topics in Toxicology that inform a chemical and molecular understanding and capacity to predict biological outcomes on the basis of structures and processes. The overarching goal of activities reported in the Journal are to provide knowledge and innovative approaches needed to promote intelligent solutions for human safety and ecosystem preservation. The journal emphasizes insight concerning mechanisms of toxicity over phenomenological observations. It upholds rigorous chemical, physical and mathematical standards for characterization and application of modern techniques.
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The Intercalator Ethidium Bromide Generates Covalent Adducts at Apurinic/Apyrimidinic Sites in DNA. Mitochondrial Dysfunction in Environmental Toxicology: Mechanisms, Impacts, and Health Implications. Practical Aspects of Flavin-Containing Monooxygenase-Mediated Metabolism. Deploying Validated Mass Spectrometry for Frontline Detection and Treatment of Human Poisoning by Long-Acting Anticoagulant Rodenticides. Issue Editorial Masthead
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