In this work, the most discriminating synthesis-related impurities found in samples from seizures and controlled synthesis of the synthetic cannabinoid MDMB-CHMICA (methyl (S)-2-(1-(cyclohexylmethyl)-1H-indole-3-carboxamido)-3,3-dimethylbutanoate) were characterized. Based on 61 available powder samples of MDMB-CHMICA, 15 key-impurities were assessed, isolated in larger quantities via flash chromatography and structurally elucidated and characterized via high resolution mass spectrometry and nuclear magnetic resonance spectroscopy. Apart from verifying the relation of the impurities to the major component, the interpretation of their chemical structures with distinct structural elements provided first insights into the manufacturing process and the precursor compounds used. Following liquid chromatography mass spectrometry analysis of the 15 key-impurities, the 61 seized samples of MDMB-CHMICA were evaluated and classified via multivariate data analysis based on the corresponding relative peak areas. In a second part of this work, stability tests and multiple controlled syntheses of MDMB-CHMICA were carried out to better understand variations in impurity signatures and to assess the significance of variations in the impurity patterns of seized samples. The last coupling step of the amino acid with 1-(cyclohexylmethyl)-1H-indole-3-carboxylic acid was performed using the coupling agents oxalyl chloride, thionyl chloride, and HATU. Furthermore, the impact of reaction time and temperature on the impurity profile were investigated. Overall, eight new impurities were found in the controlled syntheses and two degradation products of MDMB-CHIMCA were found in the course of the stability tests. Replicates of a synthesis conducted on the same day showed similar impurity signatures; on different days they showed discriminable signatures. The use of different coupling reagents or conditions gave clearly distinguishable impurity signatures.