Kinetic study of the reaction of sulfamethoxazole and glucose under acidic conditions: I. Effect of pH and temperature.

The kinetics of the reaction of sulfamethoxazole (SMX) in 5% w/v glucose to form the corresponding alpha- and beta-glucosylamines over the pH range of 0.80-6.88 at 37 degrees C has been investigated. The identity of the glucosylamines was determined by 1H-nuclear magnetic resonance spectroscopy of an authentic sample of the alpha-glucosylamine (USP) and the reaction products, and by interconversion of this compound to the corresponding beta-anomer. The reaction followed pseudo first-order reversible kinetics and involved specific acid and general acid-base catalysis. The pH-rate profile demonstrated that over the pH range of 0.80-2.90 and 5.50-6. 88 the reactions were dependent on H(+) concentration but pH independent between pH 3.00-5.45, which reflects the influence of ionization of SMX and the glucosylamines on the reversible reaction. Interpretation of the data with respect to kinetic models and rate equations for the formation and hydrolysis of the glucosylamines was investigated. Temperature dependence studies followed the Arrhenius equation with an Ea of 49.28 kJ mol(-1) for the forward and 63.46 kJ mol(-1) for the reverse reaction at pH 2.89 respectively.