The stability of streptomycin.

The biological inactivation of streptomycin in acid and alkaline solution was first noted by Waksman and his coworkers (1). In a recent review, Waksman and Schatz (2) reported that solutions of crude streptomycin maintained their original potency during 15 to 17 days at 37’, but at 100’ about 50 per cent of the activity was lost in 10 minutes. However, the pH of the solutions was not indicated. Other investigators concerned with degradation studies have described the products obtained by acid and alkaline hydrolysis of streptomycin. Folkers et al. (3-5) and Carter et al. (6) have shown that, on acid hydrolysis, streptomycin is cleaved into two basic fractions, streptidine, 1,3-diguanido-2,4,5,6-tetrahydroxycyclohexane (7, 8), and streptobiosamine. On acid hydrolysis the latter compound yields N-methyl-L-glucosamine (5), and an alkaline hydrolysis of streptidine yields streptamine, 1,3-diamino-2,4,5,6-tetrahydroxycyclohexane (7,s). The rapid inactivation of streptomycin in N sodium hydroxide was indicated by Carter et al. (9). When the hydrolysis of streptomycin hydrochloride was carried out in N sodium hydroxide at 100” or for a longer period at 40”, a substance was isolated and characterized as malt01 (10). The present investigations were carried out to determine the effect of pH and temperature on commercial and pure streptomycin sulfate. The ranges covered in these experiments are summarized in Table I. Although streptomycin in aqueous solution is sensitive to acids, bases, and heat, it has been found that its optimum stability lies between pH 3 and 7, at temperatures at or below 28”.