Synthetic cannabinoid receptor agonists in oral fluid: development of a dispersive liquid–liquid microextraction method with liquid chromatography–mass spectrometry detection

Synthetic cannabinoid receptor agonists (SCRA) comprise a class of new psychoactive substances (NPS) that rank second in terms of notified substances to the United Nations Office on Drugs and Crime. Moreover, SCRA are the most prevalent NPS in Brazilian territory. Given the risks they pose to public health, there is a pressing need to develop simple and rapid sample preparation methods in alternative biological matrices that are easy to handle and collect, such as oral fluid (OF). In this study, dispersive liquid-liquid microextraction was employed to determine 12 SCRAs in OF. For 200 µl of the sample (mixture of OF and Quantisal™ buffer), 200 µl of ice-cold acetonitrile was used as the dispersive solvent, and 100 µl of ethyl acetate was used as the extraction solvent. The limits of detection ranged from 0.5 to 2 ng/mL, while the limits of quantification were 2 ng/mL for ADB-FUBIATA and 1 ng/mL for the other analytes. The working range was 1-100 ng/mL, except for ADB-FUBIATA, which had a range of 2-100 ng/mL. The coefficients of variation for quantified analytes were <11.3% for within-run precision, <12.6% for between-run precision, and <15.8% for accuracy across all controls. The developed method was applied to six suspected samples, and one sample yielded a positive result with 39.9 ng/mL of MDMB-4en-PINACA, the most prevalent SCRA in São Paulo State, Brazil.