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部署经验证的质谱法,用于一线检测和治疗长效抗凝血灭鼠剂所致人类中毒。

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

机构信息

Department of Pharmaceutical Sciences, Linus Pauling Institute and College of Pharmacy, Oregon State University, Corvallis, Oregon 97331, United States.

Jesse Brown VA Medical Center and Department of Medicine, University of Illinois College of Medicine in Chicago, Chicago, Illinois 60612, United States.

出版信息

Chem Res Toxicol. 2024 Nov 18;37(11):1769-1775. doi: 10.1021/acs.chemrestox.4c00344. Epub 2024 Oct 29.

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.

摘要

从与华法林(双香豆素)相同的天然抗凝剂衍生而来,长效抗凝血灭鼠剂(LAARs)或超级华法林在人血中的半衰期比华法林长得多(数周而非数小时),并且是同一酶,维生素 K 环氧化物还原酶成分 1 的更有效抑制剂。尽管在全球范围内有效地用作灭鼠剂,但 LAAR 在血液浓度 >10ng/mL 时会在人类中引起严重、持久、危及生命的凝血功能障碍,导致每年发生大量意外和故意中毒。为了促进在出现不明原因的严重、持久、危及生命的凝血功能障碍的患者中及时识别和定量分析 LAAR,已经开发了几种分析方法,所有这些方法均基于电喷雾液相色谱-质谱法(LC-MS)。在本文中,我们根据验证、同时检测多种 LAAR、测量单个立体异构体以及临床应用对这些 LC-MS 方法进行了评估和比较。

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