Le Daré Brendan, Allard Sophie, Bouvet Renaud, Baert Alain, Allard Pierre-Marie, Morel Isabelle, Gicquel Thomas
INSERM, INRA, CHU Rennes, Institut NuMeCan (Nutrition, Metabolism and Cancer), University Rennes, 35000, Rennes, France.
Pharmacy Service, Rennes University Hospital, 35000, Rennes, France.
Int J Legal Med. 2020 Jan;134(1):251-256. doi: 10.1007/s00414-019-02062-9. Epub 2019 Apr 17.
Acebutolol is a β1-selective adrenergic receptor antagonist with moderate membrane-stabilizing activity and intrinsic sympathomimetic activity; accordingly, the drug is indicated in hypertension, angina pectoris, and arrhythmia. However, acebutolol's beta-blocking properties also extend the QRS and QTc intervals, and may predispose the patient to ventricular tachydysrhythmia. Here, we report autopsy and toxicological findings on a fatal case of acebutolol self-poisoning in a 70-year-old woman. Toxicological analyses of post-mortem samples (using a liquid chromatography high-resolution mass spectrometry (LC-HR-MS) method) highlighted high concentrations of acebutolol and its metabolite diacetolol in femoral blood (92.8 mg/L and 21.2 mg/L, respectively) and other matrices (cardiac blood, urine, bile, and gastric contents). A molecular networking approach provided useful information on acebutolol's metabolism and revealed the existence of an unknown phase II metabolite of acebutolol. Molecular networking also facilitated visualization of the complex LC-HR-MS/MS datasets and the sample-to-sample comparisons that confirmed massive acebutolol intoxication by ingestion.
醋丁洛尔是一种β1选择性肾上腺素能受体拮抗剂，具有中等程度的膜稳定活性和内在拟交感活性；因此，该药物适用于治疗高血压、心绞痛和心律失常。然而，醋丁洛尔的β受体阻断特性也会延长QRS和QTc间期，并可能使患者易患室性快速性心律失常。在此，我们报告一例70岁女性醋丁洛尔自服中毒致死病例的尸检和毒理学结果。死后样本的毒理学分析（采用液相色谱高分辨率质谱法（LC-HR-MS））显示，股静脉血中醋丁洛尔及其代谢物双醋洛尔浓度很高（分别为92.8mg/L和21.2mg/L），其他基质（心脏血液、尿液、胆汁和胃内容物）中也是如此。分子网络方法为醋丁洛尔的代谢提供了有用信息，并揭示了醋丁洛尔一种未知的II期代谢物的存在。分子网络还便于直观呈现复杂的LC-HR-MS/MS数据集以及样本间比较，证实了因摄入导致的大量醋丁洛尔中毒。
