Determination of the bioavailability of the quaternary compound trospium chloride in man from urinary excretion data

For the quaternary compound trospium chloride (Spasmex) which is used as an anticholinergic agent a new sensitive assay method has been developed that allows the quantitative determination of the drug in human urine and plasma. Using this method it was possible to obtain pharmacokinetic data from plasma levels and urinary excretion, and to determine the bioavailability in man. Quantitative determination is performed by alkaline hydrolysis to the corresponding spiroalcohol, ion-pair extraction with dipicrylamine, subsequent derivatization with the fluorophor benoxaprofen chloride, and ion-pair chromatographic separation on a reversed-phase column with chloride as the counter-ion using a mixture of acetonitrile and water. In healthy volunteers (n = 6) the plasma concentration time curve after intravenous administration of 0.5 mg trospium chloride could be described by an open two-compartment model. The mean half-lives were 2.7 and 97 min, respectively. After oral administration of 10 mg the highest concentration found in plasma was 1.4 ng trospium chloride/ml. 55% of the given dose were excreted unchanged into urine within 48 h after i.v. administration, the corresponding value after oral administration was 1.6%. If no hydrolysis is carried out in urine samples the spiroalcohol can be detected as metabolite of trospium. Within 48 h after i.v. administration 4% and after oral administration 0.3% of the given dose are excreted into urine as spiroalcohol. From the cumulative excretion of trospium into urine within 48 h a mean bioavailability of 2.9% was calculated.