Determination of Pancuronium Bromide and Its Metabolites in Human Urine by Dye-Extraction Method-Relation between the Extractability and Structure of Quaternary Ammonium Ions

Abstract

Pancurofnium bromide and its deacetylated metabolites were determined in human urine after intravenous administration to five patients by two methods : ion-pair extraction with bromophenol blue for the quaternary nitrogen and hydroxamic acid method for the acetyl group. Succinylcholine which was administered simultaneously was confirmed not to be extracted as the ion-pair complex at all. For the assay of the acetyl group, pancuronium and its metabolites were isolated from the urine as the ion-pair complex followed by column chromatography. The extracts were also subjected to silica gelthin-layer chromatography, wherein pancuronium and its three deacetylated metabolites could be separated while the dye went away to the top of the plate. The results revealed that approximately 20 to 50% of the dose was recovered in the urine during 24 hr period after administration, mostly in the first 3 to 4 hr period, and that pancuronium was excreted mainly as the unchanged form with a slight amount of its mono- and dihydroxy metabolites. The extractability of quaternary ammonium ions with a wide variety of structure as ion-pair complex with bromophenol blue was examined in order to find any relation to the structure. It was revealed that the extractability is determined mainly by two factors, that is, the lipophylic character of the ammonium ion and the steric effect around the cationic head and the value of the sum of π-constants for four groups plus that of E_s parameters for three smallest groups can provide an approximate measure for predicting the extractability.