A.P. Arzamastsev Department of Pharmaceutical and Toxicological Chemistry, I.M. Sechenov First Moscow State Medical University (Sechenov University), 2-4 Bolshaya Pirogovskaya Street, Moscow 119991, Russian Federation.
Department of Acute Poisonings and Somatopsychiatric Disorders, N.V. Sklifosovsky Research Institute for Emergency Medicine, 3 Bolshaya Sukharevskaya Square, Moscow 129090, Russian Federation.
J Anal Toxicol. 2022 Feb 14;46(1):e42-e47. doi: 10.1093/jat/bkab019.
Veratrum poisonings are described in the toxicology literature as multiple Veratrum species grow in different parts of the Northern Hemisphere and are occasionally ingested by mistake. Veratrum toxicity is attributed to the steroidal alkaloids contained in all parts of the plant. In Russia, Veratrum poisonings are more common since there is an over-the-counter Veratrum lobelianum-based tincture, Veratrum Aqua (VA), which is topically used for the treatment of lice infestation. Despite its toxicity, VA is misused in traditional medicine as a remedy for alcohol use disorder. We describe four cases of VA poisoning that occurred in Moscow, Russia. Three main V. lobelianum alkaloids (jervine, protoveratrine A (proA) and protoveratrine B) were determined in patient plasma and urine samples using liquid chromatography-tandem mass spectrometry (LC-MS-MS). Here, we describe a novel validated LC-MS-MS method for jervine and proA quantification. A simple and rapid liquid-liquid extraction with methyl tert-butyl ether was utilized for analyte extraction. Chromatographic separation was achieved using a Poroshell 120 EC-C18 column, and the total run time was 14 min. The lower limit of quantification was 0.1 ng/mL for jervine and proA in both plasma and urine. Biological samples were obtained upon hospital admission and during treatment, thus enabling to get a better understanding of the alkaloid elimination profile. Upon admission, plasma concentrations of jervine (concentration range: 0.10-5.01 ng/mL) prevailed over proA (concentration range: 0-0.67 ng/mL). At this time, proA already reached maximum concentrations in urine (concentration range: 0.15-37.70 ng/mL). Maximum concentrations of jervine in urine were observed 24 h after admission (concentration range: 0.10-9.55 ng/mL). In all cases, plasma concentrations of Veratrum alkaloids correlated with condition severity. Since none of the patients confirmed VA intake, instrumental analysis was the basis for the definitive diagnosis of VA poisoning.
藜芦毒素中毒在毒理学文献中有描述，因为多种藜芦属植物生长在北半球的不同地区，偶尔会被误食。藜芦毒素是由植物各部位所含的甾体生物碱引起的。在俄罗斯，藜芦毒素中毒更为常见，因为有一款非处方藜芦定基酊剂，名为藜芦水（VA），它被局部用于治疗虱子感染。尽管 VA 具有毒性，但在传统医学中被错误地用作治疗酒精使用障碍的药物。我们描述了俄罗斯莫斯科发生的 4 例 VA 中毒病例。使用液相色谱-串联质谱法（LC-MS-MS）在患者的血浆和尿液样本中确定了三种主要的藜芦定生物碱（藜芦碱、原藜芦定 A（proA）和原藜芦定 B）。在这里，我们描述了一种新的经过验证的用于藜芦碱和 proA 定量的 LC-MS-MS 方法。利用甲基叔丁基醚进行简单快速的液-液萃取进行分析物提取。采用 Poroshell 120 EC-C18 柱进行色谱分离，总运行时间为 14 分钟。藜芦碱和 proA 在血浆和尿液中的定量下限均为 0.1ng/mL。生物样本是在入院时和治疗期间获得的，因此能够更好地了解生物碱的消除情况。入院时，藜芦碱的血浆浓度（浓度范围：0.10-5.01ng/mL）高于 proA（浓度范围：0-0.67ng/mL）。此时，proA 已在尿液中达到最大浓度（浓度范围：0.15-37.70ng/mL）。入院后 24 小时观察到藜芦碱在尿液中的最大浓度（浓度范围：0.10-9.55ng/mL）。在所有情况下，藜芦生物碱的血浆浓度与病情严重程度相关。由于没有患者确认摄入 VA，因此仪器分析是 VA 中毒明确诊断的基础。
