Banminth and a Common Fragment Assay

Abstract

Abstract The metabolism of the anthelmintic pyrantel, Banminth™ (trans-l-methyl-l,4,5,6-tetrahydro- 2-[2-(2-thienyl)vinyl]pyrimidine) is characterized by extensive transformations. Evidence derived from excreted metabolites indicated nearly total destruction of the thiophene ring. The tetrahydropyrimidine moiety was less extensively degraded since the basic skeleton, iV-methylpropanediamine, was obtained after hydrolysis. In addition, some of the pyrantel radioactivity was degraded to small fragments and re-incorporated into normal tissue constituents since liver amino acids gave 14C02 after ninhydrin treatment. Attempts to develop a tissue residue assay involved the difficult task of distinguishing drug-related front tissue re-incorporated radioactivity in the parts per million range. An approach to choosing a marker residue was to select a feature common to the metabolites present in tissues, chemically liberate that entity, and designate it the marker residue. The tetrahydropyrimidine portion of pyrantel offered such an opportunity since N-methylpropanediamine was readily liberated by hydrolysis. It was demonstrated that approximately half of the radioactivity in long-term tissues was associated with N-methylpropanediamine and that the remainder of tissue radioactivity was re-incorporated label. Thus, for assay purposes, the hydrolysis of tissue followed by the quantitation of N-methylpropanediamine served as a useful procedure that permitted monitoring a number of drug-related residues which still contain the diamine moiety.