Electric field-assisted multiphase extraction to increase selectivity and sensitivity in liquid chromatography-mass spectrometry and paper spray mass spectrometry

Abstract In this work, for the first time, chromatographic paper was used for a multiphase extraction assisted by an electric field (MPEF) and directly coupled to paper spray mass spectrometry (PS-MS). Using this approach, five tricyclic antidepressants (TCAs) were determined in oral fluid. Firstly, the MPEF conditions were optimized using liquid chromatography-mass spectrometry (LC-MS/MS). The effects of the chromatographic paper and the types of electrolyte used in the acceptor phase, the organic solvent type and the amount used in the donor phase, the extraction time, and the applied electric potential were all investigated. After optimization, the analytes were extracted from the donor solution (sample and acetonitrile 1:1 (v/v)) over a period of 10 min at 300 V, crossing the free liquid membrane (1-octanol) and reaching the acceptor phase (chromatographic paper wetted with 400 mmol L-1 acetic acid). The method using LC-MS/MS was validated, demonstrating a linear range from 2 to 12 ng mL-1, with detection and quantification limits of 0.13–0.25 and 0.44–0.84 ng mL-1, respectively, an intraday precision of less than 20%, and no matrix effect observed. The optimized MPEF conditions were then applied to determine TCAs by PS-MS and for this analysis cyclobenzaprine was used as an internal standard. The easy, fast and direct approach of coupling MPEF with PS-MS analysis, as well as the pre-concentration and the low standard deviation of replicates (less than 20%), demonstrates that this method can be useful for screening in clinical and toxicological analysis.