On the Stability of Adrenaline in Injections: A Comparison of Chemical and Bioassay Methods

Abstract

Abstract The stability of adrenaline in some injections has been investigated by chemical assays based on determinations of adrenochrome and of adrenolutine, while the rat blood pressure method and the rat uterus inhibition method served as biological control procedures. The colorimetric method, in which adrenaline is oxidised to adrenochrome by means of potassium ferricyanide in acid solution, proved unable to detect any deterioration of adrenaline in procaine and adrenaline injections. The corresponding fluorimetric method, in which the adrenochrome formed is rearranged to adrenolutine by addition of strong alkali, gave results which agreed well with the biological results. In injections, adjusted to pH 3 with hydrochloric acid, adrenaline was stable for at least 20 months at 4° in solutions heated at 120° for 20 min., at 100° for 20 min. or unheated. Replacement of the hydrochloric acid by sodium metabisulphite (pH 3·6) prevented the discoloration. In injections of procaine and adrenaline, adjusted to pH 3 with hydrochloric acid, the adrenaline content decreased over the 20 month period, and was most pronounced in the solutions that had been heated before storage. Sodium metabisulphite significantly increased the stability of adrenaline in these injections and also prevented any colour formation.