Abstract: A molecularly imprinted solid phase extraction (MISPE) method has been developed for the rapid screening of metformin. Newly synthesized molecularly imprinted polymer (MIP) particles were slurry-packed into a micro-column for selective solid phase extraction (SPE) of metformin. With CH3CN flowing at 0.5 ml/min, a total binding capacity of 1600 ng metformin was determined for the 20 mg of MIP particles. A broad range of MISPE conditions was evaluated with respect to sample solvent, pH, and buffer compositions. A 95+/-2% binding could be achieved from one 20-mul injection of sample solution in acetonitrile plus phosphate buffer, up to 1200 ng of metformin. However, the micro-column interacted indiscriminately with phenformin, a structural analogue, to attain 49+/-2% binding. Separation of phenformin from metformin was ultimately achieved, using differential pulsed elution (DPE) with 1 M trifluoromethacrylic acid in acetonitrile. Final pulsed elution (FPE) using 3% trifluoroacetic acid in methanol was good for the quantitative elution of metformin. The MISPE-DPE-FPE method, with UV detection at 240 nm, afforded a detection limit of 0.8 mug/ml (or 16 ng) for metformin. Each MISPE-DPE-FPE analysis required less than 5 min to complete. (C) 2003 Elsevier B.V. All rights reserved