Optimization of Parallel Artificial Liquid Membrane Extraction for the Determination of Over 50 Psychoactive Substances in Oral Fluid Through UHPLC–MS/MS

Over the past decade, there has been a diversification of the psychoactive substances available among drug users, resulting in the expansion of a dynamic market of synthetic molecules that are challenging for drug of abuse testing. Multiclass analytical methods are useful to deal with these new psychoactive substances (NPS), but sample preparation can be difficult and generate significant amounts of chemical waste. The aim of this work was the development of a high-throughput microextraction method for the determination of 56 drugs belonging to different pharmacological classes in oral fluid (OF), including both traditional drugs and NPS. In the proposed workflow, the OF sample is cleaned-up by parallel artificial liquid membrane extraction (PALME) and analyzed by liquid chromatography–tandem mass spectrometry (LC–MS/MS). Two hundred microliters of OF are mixed with 1800 μL of carbonate buffer 0.5 M (pH 12) and 0.4 g of sodium chloride and inserted into a donor plate; the acceptor plate embed a dodecylacetate-supported liquid membrane and an acceptor solution composed of 50 μL formic acid 0.1% in H2O: MeOH, 80:20 (v/v); the whole assemblage is placed on an orbital shaker for 120 min for extraction. A full factorial design has been employed for extraction optimization to make it suitable for LC–MS/MS. The developed method is an example of green chemistry and may be used for screening and quantitative purposes, with limits of detection ranging from 0.01 to 1.5 ng mL−1 and optimal performance in term of precision and accuracy for 49 out of 56 drugs tested.