96-well pipette tips with a chemically bonded monolithic methacrylate sorbent plug were used for solid-phase extraction (SPE) of pindolol and metoprolol in human plasma samples. The sorbent plug was formed by in situ polymerization. Monolithic packed 96-tips are a tool for miniaturized, solid-phase extraction. Using such packed 96-tips, a 96-well plate could be handled in about 2 min. The key aspect of the monolithic phase is that monolithic material can provide both relatively good binding capacity and relatively low backpressure properties. The validation of the methodology showed that the accuracy values of quality-control samples were between 101% and 103% for metoprolol, while between 94% and 114% for pindolol. The precision ranged from 4% to 15%. The standard calibration curves were obtained within the concentration range 5-5000 nM in plasma samples. The coefficients of determination (R2) for plasma samples were >or=0.99. Our prepared polymer based monolithic packed 96-tips were compared with commercial silica based 96-tips and protein precipitation.