DEGRADATION OF TOBRAMYCIN IN AQUEOUS-SOLUTION

The kinetics of degradation of tobramycin (Ne-De-Ka) in aqueous solution was studied as a function of pH. Tobramycin hydrolyzes in acidic solution to yield kanosamine (Ka-OH) and nebramine (Ne-De-OH) with a pseudo first-order rate constant of 2.7 x 10(-6) s-1 in 1 N HCl at 80-degrees-C. The activation energy for the acid catalyzed hydrolysis is 32 kcal mol-1. In basic solution, the hydrolysis products are deoxystreptamine (De-OH), nebramine (Ne-De-OH) and deoxystreptamine-kanosaminide (HO-De-Ka). The pseudo first-order rate constant for the hydrolysis in 1 N KOH is 1 x 10(-8) s-1 at 80-degrees-C. The activation energy for the base catalyzed hydrolysis is 15 kcal mol-1. Tobramycin is very stable towards hydrolysis at neutral pH; however, it rapidly oxidizes giving several products including De-OH, Ne-De-OH, and HO-De-Ka. In pH 7 phosphate buffer (0.01 M), the t90 value is 70 hr at 80-degrees-C.