Abstract: This study was performed to determine the metabolic profile of four amide synthetic cannabinoids that recently abused, i.e., ADB-4en-PINACA, 4CN-CUMYL-BUTINACA, 5F-EMB-PICA and 4F-MDMB-BUTICA, in human liver microsomes (HLMs). The four amide synthetic cannabinoids were added to the microsomal incubation model, being incubated for 10 min, 60 min or 3 h to simulate human hepatic metabolism.Liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) analytical instrument was employed to determine and speculate the structure of phase I metabolites and their possible metabolic pathways.The results showed that there were 27 phase I metabolic pathways for the four amide synthetic cannabinoids, including hydroxylation, carboxylation, N-dealkylation and ester hydrolysis, with the main phase I metabolic pathways of ester hydrolysis, dihydrodiol (pentenyl tail), oxidative defluorination to carboxylic acid, monohydroxylation (alkyl side chain or indole/indazole ring) and N-dealkylation.The results of this study may provide potential detection markers for forensic identification and sewage abuse assessment of the four amide synthetic cannabinoids.