Detection of the Synthetic Cannabinoids AB-CHMINACA, ADB-CHMINACA, MDMB-CHMICA, and 5F-MDMB-PINACA in Biological Matrices: A Systematic Review

SIMPLE SUMMARY: Synthetic cannabinoids were originally developed for scientific research and potential therapeutic agents. However, clandestine laboratories synthesize them and circumvent legal barriers by falsely marketing them as incense or herbal products. They have serious adverse effects, and new derivatives are continuously found in the market, making their detection difficult due to the lack of comparative standards. Human matrices are used to identify the type of synthetic cannabinoid and the time of its consumption. This review discusses the use of hair, oral fluid, blood, and urine in the detection and quantification of some of the major synthetic cannabinoids. Based on the results, some recommendations can be followed, for example, the use of hair to detect chronic and retrospective consumption (although sensitive to external contamination) and oral fluid or blood for the simultaneous detection of the parent compounds and their metabolites. If longer detection times than blood or oral fluid are needed, urine is the matrix of choice, although its pH may intervene in the analysis. This work highlights the use of new techniques, such as high-resolution mass spectrometry, to avoid the use of previous standards and to monitor new trends in the drug market. ABSTRACT: New synthetic cannabinoids (SCs) are emerging rapidly and continuously. Biological matrices are key for their precise detection to link toxicity and symptoms to each compound and concentration and ascertain consumption trends. The objective of this study was to determine the best human biological matrices to detect the risk-assessed compounds provided by The European Monitoring Centre for Drugs and Drug Addiction: AB-CHMINACA, ADB-CHMNACA, MDMB-CHMICA, and 5F-MDMB-PINACA. We carried out a systematic review covering 2015 up to the present date, including original articles assessing detection in antemortem human biological matrices with detailed validation information of the technique. In oral fluid and blood, SC parent compounds were found in oral fluid and blood at low concentrations and usually with other substances; thus, the correlation between SCs concentrations and severity of symptoms could rarely be established. When hair is used as the biological matrix, there are difficulties in excluding passive contamination when evaluating chronic consumption. Detection of metabolites in urine is complex because it requires prior identification studies. LC-MS/MS assays were the most widely used approaches for the selective identification of SCs, although the lack of standard references and the need for revalidation with the continuous emergence of new SCs are limiting factors of this technique. A potential solution is high-resolution mass spectrometry screening, which allows for non-targeted detection and retrospective data interrogation.