Metabolic products of the cinchona alkaloids in human urine.

In spite of the wide use of quinine in the treatment of malaria, and of quinidine in the therapy of cardiac arrhythmias, little information exists concerning the metabolic fate of the cinchona alkaloids administered to man. As early as 1869, Kerner (1) isolated from the urine of subjects receiving quinine a substance thought to be quinetine, a derivative of quinine in which the vinyl side chain of the quinuclidine nucleus has been oxidized to a carboxyl group. Halberkann (2) suggested that the compound was not a metabolite of quinine but had been formed by oxidation during the analytical procedure. Nierenstein (3) also claimed to have isolated quinetine from the urine of a single subject receiving quinine. In addition this investigator isolated from the urine of subjects with blackwater fever a product that exhibited marked hemolytic properties for red blood cells and that appeared to account for the symptoms of the disease (4). This substance, hemoquinic acid, was characterized as 6methoxyquinoline-4-ketocarboxylic acid. Lipkin (5) obtained a product by incubation of quinine with minced sheep liver which, on the basis of its chemical properties, he considered quinetine. Kelsey, Geiling, Oldham, and Dearborn (6) isolated a different type of metabolic product when quinine was incubated with rabbit liver. This derivative was a phenol whose structure was characterized by Mead and Koepfli (7) as a carbostyril in which the quinoline nucleus had been oxidized in position 2.