Notwithstanding the continuous progress in instruments playability and impressive potential of modem LC-MS based bio-analytical methodologies, sample preparation still remains as the key technical bottleneck step, mainly due to the time-consuming and error-prone process that is highly dependent on the analyte nature and the matrix type.Nowadays, there is a clear trend in the field of residue analysis toward the use of a straightforward generic method to cover a broad array of analyte/matrix combinations by the simultaneous extraction of a vast number of target compounds (multi-analyte) from various types of sample matrixes (multi-matrix) in a single procedure.