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Journal of Pharmacology And Experimental Therapeutics, Vol. 165, Issue 1, 14-22, 1969
Copyright © 1969 by American Society for Pharmacology and Experimental Therapeutics

A SPECIFIC AND SENSITIVE ASSAY FOR AMINOGUANIDINE: ITS APPLICATION TO A STUDY OF THE DISPOSITION OF AMINOGUANIDINE IN ANIMAL TISSUES

M. A. BEAVEN 1, J. W. GORDON 1, S. JACOBSEN 1, and W. B. SEVERS 1

1 Laboratory of Chemical Pharmacology, National Heart Institute, National Institutes of Health, Bethesda, Maryland

A colorimetric assay for aminoguanidine is described. The assay is based on the reaction of aminoguanidine with p-nitrobenzaldehyde in acid solution to form a product having an intense yellow color. This product is separated from interfering substances by extraction into ethyl acetate and then back into an aqueous phase of dilute HCl. The HCl extract is made alkaline, and the yellow product is assayed spectrophotometrically. Values for reaction and tissue blanks are near zero, and as little as 0.1 µg of aminoguanidine can be measured by the procedure. Chromatographic studies revealed that the assay is specific for aminoguanidine. Studies in rats showed that aminoguanidine given by i.v. injection rapidily leaves the circulation and accumulates in many tissues except brain. The drug accumulates to the greatest extent in liver, kidney, submaxillary gland and tissues of the gastrointestinal tract. Although aminoguanidine is localized in an unbound form in the soluble portion of tissue cells, it does not readily pass back into the circulation and disappears from tissues at a relatively slow rate. Thus, 2 hr after the injection of drug, the tissue/plasma concentration ratios are 18 for submaxillary gland, 13 for kidney and 4 or higher for other tissues tested except for brain. The degree of aminoguanidine accumulation in a tissue appears to be linearly related to dose.

Submitted on May 21, 1968
Accepted on September 16, 1968




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