Degradation of tobramycin in aqueous solution

Abstract

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 × 10^?6 s^?1 in 1 N HCl at 80°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 × 10^?8 s^?1 at 80°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°C.