A capillary solid-phase extraction (SPE) system has been coupled directly to electrospray tandem mass spectrometry for quantification of free tolterodine and metabolite concentrations in plasma. The unbound fraction of these compounds was obtained by ultrafiltration of plasma. The ultrafiltrate was directly injected onto the SPE capillary (4 mm x 200 microm, 5 microm C18). After desalting and clean-up of the sample, the analytes were eluted in backflush mode with methanol-1 mM triethylamine (70:30, v/v), providing considerable solute focusing. Elution from the SPE capillary was improved by inserting a short trapping capillary between the SPE capillary and the MS interface, by which analyte focusing was increased. The unresolved compounds eluted simultaneously with the remaining matrix compounds and were detected in a multiple-reaction monitoring (MRM) mode. No interference of the sample matrix on detection was observed, allowing aqueous standards to be used for calibration. Linear calibration curves were obtained between 0.05 and 1000 ng/ml (corresponding to 150 pM-3 microM) and the limit of detection was 50 pg/ml injecting 10 microl. Equilibration of the SPE capillary, sample loading, elution and detection took less then 6 min per sample.