| 2C series derivatives are a type of new psychoactive substance widely abused worldwide due to their dual hallucinogenic and excitatory effects.However,the rapid evolution of the chemical structures of these substances has poster significant challenges for drug control work.Specifically,the lack of standard testing protocols and systematic research on the metabolic pathways of 2C series derivatives has hindered the accurate identification of these substances and their metabolites in biological samples.Therefore,conducting comprehensive studies on the metabolic processes of 2C series derivatives,including metabolite analysis,inference of metabolic pathways,and identification of metabolic markers,is essential.These efforts will establish reliable testing methods for detecting 2C series derivatives in biological samples and combat their illegal use.To achieve these objectives,this article aims to establish in vitro and in vivo models for six common 2C series derivatives using human liver microsomes and rats,respectively.The study will simulate the metabolic processes of humans,and analyze the in vitro and in vivo metabolites of the six derivatives using ultra high-performance liquid chromatography quadrupole time of flight mass spectrometry(UPLC-Q-TOF/MS).Based on the signal response intensity,the study will screen for metabolic biomarkers and infer the metabolic pathways of the 2C series derivatives.These findings will provide crucial insights for the development of accurate detection methods for these substances in biological samples,ultimately contributing to the effective monitoring and prevention of 2C series derivative crimes in drug control efforts.1.A review was provided regarding the structure and classification of 2C series derivatives,as well as an overview of the methods used for detecting and quantitatively analyzing these derivatives in biological and in vitro samples.Additionally,an identification model for in vivo and in vitro metabolites,as well as the metabolic laws of2 C series derivatives,was summarized.This research offers valuable information that can be utilized as a reference for clinical studies and forensic toxicological analysis of 2C series derivatives and their metabolites.2.An analytical method using UPLC-Q-TOF/MS for detecting six 2C series derivatives was established.Through analysis of the fragmentation rules and characteristic fragment ions of the original drug,this research provided an experimental basis for the structural analysis of metabolites in human liver microsome incubation experiments and rat animal experiments.3.An in vitro incubation model of human and rat liver microsomes was established to simulate the metabolic environment in vivo.In vitro analysis of the metabolites of six 2C series derivatives was conducted,and the results revealed that all six derivatives produced phase Ⅰ and Ⅱ metabolites.The main metabolic pathways of phase I included monohydroxylation,di-hydroxylation,O-demethylation,O-demethylation and Ndemethoxybenzylation,while the primary metabolic pathway of phase Ⅱ was glucuronidation.The main metabolites were found to be the O-demethylated metabolites,based on a comparison of the signal response intensity of metabolites.4.The in vivo metabolites of six 2C series derivatives were analyzed and verified in rats.The study compared the metabolites produced in vivo and in vitro by human liver microsome incubation and rat metabolic models,and the metabolic pathways of the six derivatives were analyzed.The results demonstrated that all six derivatives produced phase Ⅰ and Ⅱ metabolites,including mono-hydroxylation,dihydroxylation,O-demethylation,and N-demethoxybenzylation as the main metabolic pathways of phase Ⅰ,gluconaldehyde was identified as the primary metabolic pathway of phase Ⅱ.Based on a comparison of the signal response intensity of metabolites,the O-demethylated metabolites and Odemethylated + hydroxylated metabolites were identified as significant metabolic markers. |
