Commercial monolithic columns were evcluated as extraction supports for the analysis of various drugs and their metabolites from plasma. For this purpose, a precolumn packed with a monolithic phase was used as extraction and enrichment support and integrated in a column-switching system for the direct and simultaneous analysis of fluoxetine and norfluoxetine, methadone and EDDP, flunitrazepam and norflunitrazepom in humon plasma. In this configuration, plasma samples were directly injected onto a Chromolith Flash precolumn (25×4.6 mm I.D.) coupled to a microbore analytical column packed with a conventional reversed-phase malerial. Detection was by an electrospray-ionization mass spectrometer (ESl-MS). Total analysis time, including extraction and separation of the six analytes, was <10 min. For all the investigated compounds, the limits of quantitation (LOQ) were estimated in the ng.mL1 range for an injection volume of 50 μL. The method was also applied to a real clinical case to demonstrate its applicability.