On the deterioration of crystalline strophanthin in aqueous solution

Abstract

For clinical use, crystalline strophanthin is commonly dissolved in normal salt solution or water and marketed in glass ampules. Sterilization is accomplished by autoclaving after the ampules have been filled and sealed. In making biologic assays, by the cat method of Hatcher and Brody, of several lots of a commercial preparation of “ouabain” (g-strophanthin) wide variations in potency were found. On adding a drop of indicator, phenol red, to the contents of those ampules showing low potency, it was observed that they were decidedly alkaline in reaction, whereas freshly prepared, aqueous solutions of the drug are neutral or slightly acid. Experiments were undertaken to ascertain the cause of the deterioration in relation to the altered hydrogen ion concentration and to devise a method for preparing a stable solution for therapeutic purposes.

Doubly distilled water, pH 6.0, was autoclaved in various types of glass bottles and flasks, chosen at random from the laboratory supply. Immediately after autoclaving, the reaction of the water in the cheaper and softer varieties of container had become quite alkaline, the pH ranging from 6.3 to 9.0. In the hard glass flasks (Pyrex) no significant alteration in reaction occurred.

A similar experiment was done with sixteen types of glass ampules, obtained from a number of pharmaceutical firms, and used by them in marketing their products. The distilled water autoclaved in these ampules in every instance showed a change in pH, which now ranged, in different lots, from 6.2 to 9.0. In order to titrate back to neutrality (pH 7.0) the most alkaline solution in the series, 2.6 C.C. of NJ5o HCl per IOO C.C. of water were required.

Next, a 2 per cent. solution of strophanthin was made in standard M/20 phosphate mixtures with pH 7.0, pH 8.6 and pH 5.0.