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有毒植物-使用液相色谱-质谱法进行快速系统临床毒理学筛选检测秋水仙碱。

Toxic plants-Detection of colchicine in a fast systematic clinical toxicology screening using liquid chromatography-mass spectrometry.

机构信息

Department of Experimental and Clinical Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, Center for Molecular Signaling (PZMS), Saarland University, Homburg, Germany.

出版信息

Drug Test Anal. 2022 Feb;14(2):377-381. doi: 10.1002/dta.3160. Epub 2021 Sep 13.

DOI:10.1002/dta.3160
PMID:34490751
Abstract

Colchicum autumnale, which can be mistaken for Allium ursinum, contains the alkaloid colchicine potentially leading to life-threatening up to fatal intoxications. We report two cases of acute intoxications with unexplained circumstances. Using the authors' systematic screening approaches, colchicine could be detected in blood plasma and urine samples using liquid chromatography coupled to linear ion trap mass spectrometry (LC-ITMS ) and high-resolution tandem mass spectrometry (LC-HRMS/MS). Metabolites of colchicine could be identified in urine for confirmation of screening results. Gas chromatography-mass spectrometry (GC-MS) analysis was also conducted, but colchicine could not be detected. Furthermore, colchicine concentration was estimated via LC-HRMS/MS in plasma samples. Results of the systematic screening indicated the ingestion of colchicine from both subjects. In both cases, the parent compound was detected in blood plasma and urine using the LC-HRMS/MS and LC-ITMS system. An O-demethylation metabolite was identified in urine samples of both subjects using LC-HRMS/MS; the N-deacetylation product was also found in urine samples of both cases via LC-HRMS/MS and LC-ITMS . The use of LC-ITMS resulted only in the detection of the O-demethylation product in case 2. Plasma concentrations were estimated at 2.5 ng/ml and 4.7 ng/ml for cases 1 and 2, respectively. We demonstrated the detection of this highly toxic alkaloid in blood plasma and urine using a time-saving and reliable clinical systematic screening. Furthermore, we identified metabolites of colchicine being rarely discussed in literature, which can be used as additional screening targets.

摘要

秋水仙(Colchicum autumnale),可能会被误认为是熊葱(Allium ursinum),其含有秋水仙碱,这种生物碱可能会导致危及生命甚至致命的中毒。我们报告了两例原因不明的急性中毒病例。通过作者的系统筛选方法,使用液相色谱-线性离子阱质谱联用(LC-ITMS)和高分辨串联质谱(LC-HRMS/MS)在血血浆和尿液样本中检测到了秋水仙碱。在尿液中鉴定到了秋水仙碱的代谢物,以确认筛选结果。还进行了气相色谱-质谱(GC-MS)分析,但未能检测到秋水仙碱。此外,通过 LC-HRMS/MS 估算了血浆样本中的秋水仙碱浓度。系统筛选的结果表明,两名受试者都摄入了秋水仙碱。在这两种情况下,均使用 LC-HRMS/MS 和 LC-ITMS 系统在血血浆和尿液中检测到了母体化合物。在两名受试者的尿液样本中均通过 LC-HRMS/MS 鉴定到了一个 O-去甲基代谢物;通过 LC-HRMS/MS 和 LC-ITMS 在两名患者的尿液样本中均发现了 N-去乙酰化产物。LC-ITMS 仅在病例 2 中检测到了 O-去甲基产物。分别估计病例 1 和 2 的血浆浓度为 2.5 ng/ml 和 4.7 ng/ml。我们使用一种节省时间且可靠的临床系统筛选方法,证明了这种高度有毒生物碱在血血浆和尿液中的检测。此外,我们鉴定到了文献中很少讨论的秋水仙碱代谢物,它们可作为额外的筛选靶标。

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