A simple and green procedure was proposed for the separation and preconcentration of ionizable analytes from complex solid-phase samples. The developed procedure was applied to the HPLC–MS/MS determination of two nonsteroidal anti-inflammatory drugs (ketoprofen and diclofenac) in beef liver samples. The procedure included two stages. The first one assumed separation of analytes from a liver sample in a sodium carbonate solution (pH 11). In this case analytes ionization promoted mass-transfer from solid sample phase to alkaline aqueous phase. The second one assumed an effervescence-assisted dispersive liquid–liquid microextraction based on deep eutectic solvent decomposition in alkaline aqueous sample phase resulting extragent and proton donor agent formation. As result, a simple effervescent reaction between proton donor agent and effervescent agent (sodium carbonate) produced carbon dioxide and assisted in a dispersion of extragent. Deep eutectic solvent consisting of menthol and formic acid (1:40 mol) provided excellent extraction of ketoprofen and diclofenac. LODs calculated from a blank test, based on 3σ, were 0.1 and 0.3 μg kg⁻¹ for ketoprofen and diclofenac, respectively.