Deterioration of Crystalline Strophanthin. 63 



37 (1497) 



On the deterioration of crystalline strophanthin in aqueous 



solution. 



By Robert L. Levy and Glenn E. Cullen. 



[From the Hospital of the Rockefeller Institute for Medical Research.] 



For clinical use, crystalline strophanthin is commonly dis- 

 solved 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 commer- 

 cial 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 N/50 HC1 per 100 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. 



