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死后生物基质中金雀花碱的测定方法及其在两起法医案件中的应用。

Method for determination of cytisine in post-mortem biological matrices and its application to two forensic cases.

作者信息

Nowak Karolina, Szpot Paweł, Zawadzki Marcin, Chłopaś-Konowałek Agnieszka

机构信息

Department of Pharmacology, Faculty of Medicine, University of Opole, 48 Oleska Street, 45052, Opole, Poland.

Institute of Toxicology Research, Borowa, Poland.

出版信息

Forensic Toxicol. 2025 Jul;43(2):385-394. doi: 10.1007/s11419-024-00710-3. Epub 2024 Dec 19.

DOI:10.1007/s11419-024-00710-3
PMID:39695055
Abstract

PURPOSE

Cytisine is the active ingredient in preparations used for smoking cessation. Its popularity is attributed to its low cost, efficacy, and low incidence of adverse effects. Additionally, its easy over-the-counter availability is also significant. This accessibility makes it a potential substance for use in suicidal attempts. The aim of this study was to develop a method for the determination of cytisine in biological material for use in clinical and forensic toxicology, and to apply this method in authentic cases.

METHODS

Biological samples were subjected to liquid-liquid extraction using cytisine-d as an internal standard. Analyses were performed using a Hydrophilic Interaction Liquid Chromatography (HILIC) column with the technique of ultra-high-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry.

RESULTS

For both matrices (blood and urine), the linear concentration range was 5-1000 ng/mL. The method met all validation requirements. The concentration of cytisine in a man taking it for smoking cessation in post-mortem materials was 21.4 ng/mL in blood, 958.9 ng/mL in urine, ca. 30 ng/mL in vitreous humor, and ca. 40 ng/mL in bile. In contrast, for a man with cytisine intoxication, the concentration was 174.6 ng/mL in blood and > 10,000 ng/mL in urine. In both cases, no N-methylcytisine was detected.

CONCLUSIONS

The developed method can be used for the determination of cytisine in post-mortem biological matrices as well as for clinical purpose. We presented the concentrations of cytisine in the post-mortem biological samples of a man taking cytisine for smoking cessation and of a man with suicidal cytisine poisoning.

摘要

目的

金雀花碱是用于戒烟制剂中的活性成分。其受欢迎的原因在于成本低、疗效好且不良反应发生率低。此外,其易于非处方获取这一点也很重要。这种可及性使其成为自杀未遂中可能被使用的物质。本研究的目的是开发一种用于临床和法医毒理学中生物材料内金雀花碱测定的方法,并将该方法应用于实际案例。

方法

生物样品以氘代金雀花碱作为内标进行液 - 液萃取。使用亲水作用液相色谱(HILIC)柱,采用超高效液相色谱与三重四极杆串联质谱联用技术进行分析。

结果

对于两种基质(血液和尿液),线性浓度范围均为5 - 1000 ng/mL。该方法满足所有验证要求。在死后材料中,一名服用金雀花碱戒烟男子的血液中金雀花碱浓度为21.4 ng/mL,尿液中为958.9 ng/mL,玻璃体液中约为30 ng/mL,胆汁中约为40 ng/mL。相比之下,一名金雀花碱中毒男子的血液中浓度为174.6 ng/mL,尿液中浓度>10000 ng/mL。在这两种情况下,均未检测到N - 甲基金雀花碱。

结论

所开发的方法可用于死后生物基质内金雀花碱的测定以及临床目的。我们展示了一名服用金雀花碱戒烟男子和一名金雀花碱自杀中毒男子死后生物样品中的金雀花碱浓度。

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Method for determination of cytisine in post-mortem biological matrices and its application to two forensic cases.死后生物基质中金雀花碱的测定方法及其在两起法医案件中的应用。
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用于高通量分析14种烟草相关化合物尿液生物标志物的自动化固相萃取和极性切换串联质谱技术
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Establishment of a High-Resolution Liquid Chromatography-Mass Spectrometry Spectral Library for Screening Toxic Natural Products.建立用于筛选有毒天然产物的高分辨液相色谱-质谱光谱库。
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Cytisine is neuroprotective in female but not male 6-hydroxydopamine lesioned parkinsonian mice and acts in combination with 17-β-estradiol to inhibit apoptotic endoplasmic reticulum stress in dopaminergic neurons.野靛碱对 6-羟多巴胺致帕金森病雌性小鼠具有神经保护作用,但对雄性小鼠没有作用,并且与 17-β-雌二醇联合作用可抑制多巴胺能神经元凋亡性内质网应激。
J Neurochem. 2021 May;157(3):710-726. doi: 10.1111/jnc.15282. Epub 2021 Jan 10.
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The World Health Organization's World No Tobacco Day 2020 Campaign Exposes Tobacco and Related Industry Tactics to Manipulate Children and Young People and Hook a New Generation of Users.世界卫生组织2020年世界无烟日运动揭露了烟草及相关行业操纵儿童和年轻人并诱使新一代使用者上瘾的手段。
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Comparison of Various Chromatographic Systems for Analysis of Cytisine in Human Serum, Saliva and Pharmaceutical Formulation by HPLC with Diode Array, Fluorescence or Mass Spectrometry Detection.高效液相色谱法-二极管阵列、荧光或质谱检测法分析人血清、唾液和药物制剂中 cytisine 的各种色谱系统比较。
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