利用液相色谱-高分辨质谱研究5F-UR-144在家兔体内的代谢产物

Metabolites of 5F-UR-144 in Rabbits by Liquid Chromatography-High Resolution Mass Spectrometry

本文分析5F-UR-144在家兔尿中的代谢物,探索其代谢方式及路径,从而建立5F-UR-144代谢物的检测方法。将家兔分为5F-UR-144组和空白对照组,采用液相色谱-高分辨质谱联用仪对肌注实验家兔的尿液经乙腈沉淀蛋白后进行检测,通过代谢软件建立代谢物筛查库,筛查出来的组分根据高分辨质谱碎片信息和结构解析软件分析其化学结构。经过仪器检测和数据分析家兔尿液中的代谢物,发现5F-UR-144通过氟基羧基化、烷基氧化羟基化和羧基化,部分与葡萄糖醛酸结合,产生了11种代谢物,并推断出其代谢路径。高分辨质谱可以准确测定化合物的分子式,通过二级碎片高分辨结果也能精确计算出碎片的化学元素组成,对比其他质谱在代谢物化学结构分析上有独特优势。该检测方法为吸食5F-UR-144案件的判定、代谢物检验和合成戒断药物提供了参考。

Since the mid-2000s synthetic cannabinoids have been abused as recreational drugs,prompting scheduling of these substances in many countries.To circumvent legislation,manufacturers have constantly marketed new compounds,5FUR-144 is one of the most recently and widely abused drugs.In order to combat drug abuse better,the metabolites of 5FUR-144 in rabbit urine were analyzed to explore its metabolic mode and pathway.Rabbits were divided into experimental group and blank group,and rabbits in the experimental group were injected with 5F-UR-144 ethanol solution,while blank ethanol solution was injected into the blank group.Acetonitrile was added to the urine of rabbits for the precipitation of protein,and the extract was detected by liquid chromatography-high resolution mass spectrometry.It was predicted of 5F-UR-144 metabolites by the metabolic software Bio Transformation Mass Defects and the possible metabolite data was compiled into a database for screening analysis.Suspected 5F-UR-144 metabolites were analyzed by secondary mass spectrometry.Based on the mass spectral fragment information measured by liquid chromatography-high resolution mass spectrometry,the molecular formula and chemical structure of unknown metabolites were analyzed using analytical software.After instrumental testing and data analysis of metabolites in rabbit urine,it was found that 5F-UR-144 produced 11 metabolites resulting from hydroxylation,carboxylation,and further glucuronidation of some oxidative metabolites.5F-UR-144 also was defluorinated,forming UR-144 metabolites.By analyzing these 11 metabolites,metabolic pathways were inferred.The formula of the intact molecule was accurately determined,and accurate mass measurements aided in assigning correct fragment structures.Structure elucidation was easier and faster than conventional MS requiring multiple injections for precursor ion,neutral loss,and product ion scans.And these are very important data on 5F-UR-144 metabolites which give clinical and forensic toxicologists a basis for developing analytical methods,identifying 5F-UR-144 exposure,and interpreting urine results.This approach provides a powerful tool for rapid identification of metabolites of unknown synthetic cannabinoids.It also had provided a reference for developing withdrawal drugs for synthetic cannabinoid addiction.