DETERMINATION OF TOLTERODINE AND THE 5-HYDROXYMETHYL METABOLITE IN PLASMA, SERUM AND URINE USING GAS-CHROMATOGRAPHY MASS-SPECTROMETRY

A specific and sensitive capillary gas chromatography-mass spectrometr y assay for the determination of tolterodine and the 5-hydroxymethyl m etabolite (Labcode DD 01) in plasma, serum and urine is described. Ext raction of the analytes was performed with liquid/liquid or solid-phas e extraction prior to derivatisation with a silyl reagent. The derivat ives were quantified by selected ion monitoring mass spectrometry usin g deuterium-labelled internal standards. A single level calibration cu rve was utilised for quantification of plasma, serum and urine concent rations of tolterodine and DD 01. The accuracy (inter-and intra-day) f or both analytes was within 87-110% in the range 0.5 and 50 ng ml(-1) and precision was better than 90%. Overall, this method was shown to b e reliable for pharmacokinetic assays of tolterodine and the metabolit e DD 01 in samples from preclinical and clinical studies. (C) 1997 Els evier Science B.V.