用GC-MS和LC-QTOF鉴别尿中4-氯甲基卡西酮代谢物

Emerging trends in drugs, addictions, and health Pub Date : 2024-12-01 DOI:10.1016/j.etdah.2023.100093

M.A. Gofenberg, V.A. Shevyrin

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引用次数: 0

摘要

合成卡西酮是在俄罗斯非法市场上发现的最常见的新型精神活性物质。1-（4-氯苯基）-2-甲基氨基丙烷-1- 1（4-氯甲基卡西酮，Clephedrone, 4-CMC）常见于急性兴奋剂中毒患者的尿样和警方怀疑在药物影响下驾车的司机的尿样中。本研究采用气相色谱-质谱联用和液相色谱-质谱联用的方法测定氯黄酮的代谢谱。方法采用两份活体尿样，寻找氯菲雄酮代谢物及其葡糖苷类。采用7890气相色谱仪，HP-5MS柱，5977质谱仪（Agilent Technologies）测定I相代谢物。一期和二期代谢产物采用液相色谱-高分辨率质谱（LC- hrms）进行鉴定，采用1290 Infinity II LC液相色谱仪，配备Zorbax Eclipse Plus C18柱和6545 Q-TOF质谱仪（Agilent Technologies）。结果在人尿中检出氯花雄酮的i、II期代谢物。生物转化的主要途径包括仲胺n -去甲基化生成去甲麻黄酮和酮段还原成羟基形成二氢麻黄酮。还鉴定了一种代谢物，它是由二氢四烯酮失去水分形成双键而获得的。次要的生物转化途径与丙基链上甲基的氧化、苯环上的羟基化以及这些反应的组合有关。大多数代谢物以游离和葡萄糖醛酸形式存在于尿液中。结论合成卡西酮是一种重要的精神兴奋剂，与驾驶障碍、中毒和致死性过量有关。4-氯甲基卡西酮的代谢研究结果可用于人工合成卡西酮急性中毒的诊断，并预测新型精神活性物质的代谢方向。

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Identification of 4-Chloromethylcathinone Metabolites in Urine with GC-MS and LC-QTOF

Introduction

Synthetic cathinones are the most common group of new psychoactive substances found on the illegal Russian market. 1-(4-Chlorophenyl)-2-methylaminopropan-1-one (4-Chloromethylcathinone, Clephedrone, 4-CMC) is regularly found in urine samples from patients with acute stimulant poisoning and urine samples obtained from drivers suspected by police of driving under the influence of drugs. The aim of the study was to determine the metabolic profile of Clephedrone by GC-MS and LC-HRMS.

Methods

Two urine samples from living individuals were used to search for Clephedrone metabolites and their glucuronides. 7890 gas chromatograph with HP-5MS column with 5977 mass spectrometer (Agilent Technologies) for determination of metabolites of I phase was used. Phase I and II metabolites were identified by liquid chromatography-high resolution mass spectrometry (LC-HRMS), which was performed on a 1290 Infinity II LC liquid chromatograph equipped with a Zorbax Eclipse Plus C18 column with a 6545 Q-TOF mass spectrometer (Agilent Technologies).

Results

I and II phase metabolites of Clephedrone have been found in human urine. The main pathways of biotransformation include N-demethylation of the secondary amine to yield norclephedrone and reduction of the ketone moiety to the hydroxyl group to form dihydroclephedrone. Also identified is a metabolite obtained by loss of water by dihydroclephedrone to form a double bond. Minor pathways of biotransformation are associated with the oxidation of the methyl group of the propyl chain, hydroxylation at the benzene ring, and a combination of these reactions. Most of the metabolites were present in the urine, both in free and glucuronated forms.

Conclusions

Synthetic cathinones are important psychostimulants that have been associated with driving disorders, intoxications, and fatal overdoses. The results of a study of the metabolism of 4-Chloromethylcathinone can be used to diagnose acute poisoning with synthetic cathinones, and to predict the directions of metabolism of new psychoactive substances.

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来源期刊

Emerging trends in drugs, addictions, and health Pharmacology, Psychiatry and Mental Health, Forensic Medicine, Drug Discovery, Pharmacology, Toxicology and Pharmaceutics (General)

CiteScore

2.40

自引率

0.00%

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