基于UPLC-Q-exactive orbitrap-MS法的新型合成大麻素4CN-MDMB-BUTINACA体外代谢研究

Investigation of metabolites of synthetic cannabinoid 4CN-MDMB-BUTINAC in vitro by liquid-chromatography-quadruple/orbitrap mass spectrometry

为研究新型合成大麻素3,3-二甲基-2-[1-(4-氰基丁基)吲唑-3-甲酰氨基]丁酸甲酯(4CN-MDMB-BUTINACA)的体外代谢产物,本研究通过体外人肝微粒体孵育模型,采用高效液相色谱串联Q exactive质谱检测合成大麻素原形药及其代谢产物。肝微粒体实验发现4CN-MDMB-BUTINACA通过羟基化、酯水解、酯水解加羟基化、戊烷氧化为戊酸反应代谢物和酯水解加戊烷氧化为戊酸反应代谢物等代谢途径共产生7种代谢产物。本研究解析了合成大麻素体外代谢途径及其代谢产物,其中羟基化反应代谢产物(M1-a)、酯水解反应代谢产物(M2)以及戊烷氧化为戊酸反应代谢物(M4)为潜在的代谢标志物。研究结果为合成大麻素4CN-MDMB-BUTINACA的司法鉴定和吸食认定提供技术支撑。

To investigate the metabolites of a new synthetic cannabinoid 3,3-dimethyl-2-[1-(4-cyanobutyl)indazole-3-formamimino]methyl butyrate(4CN-MDMB-BUTINACA) in vitro,a human liver microsome incubation model was established to analyze the metabolic biotransformation of synthetic cannabinoids using ultra-high performance liquid chromatography coupled to quadrupole-orbitrap high-resolution mass spectrometry.Nontarget metabolomic results showed that the metabolites of 4CN-MDMB-BUTINACA included hydroxylation,ester hydrolysis,ester hydrolysis with hydroxylation reaction,pentane oxidation and ester hydrolysis with pentane oxidation reaction,among which M1-a,M2 and M4 were potential metabolic markers.The research results provide a theoretical basis and technical support for the biomonitoring and metabolic characterisation of the cannabinoid 4CN-MDMBBUTINACA.