PT - JOURNAL ARTICLE AU - P C Canfell AU - N Castagnoli, Jr AU - M R Fahey AU - P J Hennis AU - R D Miller TI - The metabolic disposition of laudanosine in dog, rabbit, and man. DP - 1986 Nov 01 TA - Drug Metabolism and Disposition PG - 703--708 VI - 14 IP - 6 4099 - http://dmd.aspetjournals.org/content/14/6/703.short 4100 - http://dmd.aspetjournals.org/content/14/6/703.full SO - Drug Metab Dispos1986 Nov 01; 14 AB - This paper summarizes the results of studies of the metabolic fate of laudanosine, a major degradation product of atracurium. Intravenous bolus doses of laudanosine (1-3 mg/kg) were administered to eight dogs and two rabbits anesthetized with halothane, and urine and bile samples were collected for up to 6 hr. Urine samples also were collected from two surgical patients given repetitive doses of atracurium. Metabolites were isolated from all samples using C18-Sep Paks. Treatment of the isolates with beta-glucuronidase followed by purification of the hydrolysate by preparative liquid chromatography provided metabolite fractions which were characterized by analytical liquid chromatography and capillary gas chromatography combined with nitrogen-phosphorus and/or electron ionization-mass spectrometric detection. Reference compounds were employed as chromatographic retention time markers. O-Trimethylsilyl, O-tert-butyldimethylsilyl, and N-trifluoroacetyl derivatives of the metabolites and reference compounds were used for gas chromatographic and mass spectrometric analysis. In all three species, the following metabolites of laudanosine were identified: pseudocodamine (4'-desmethyllaudanosine), pseudolaudanine (6-desmethyllaudanosine), laudanine (3'-desmethyllaudanosine), codamine (7-desmethyllaudanosine), N-norlaudanosine, N-norpseudocodamine, and N-norpseudolaudanine.