HYDROLYSIS OF THE PRODRUG, 2',3',5'-TRIACETYL-6-AZAURIDINE

Purpose. The purposes were to study the kinetics of hydrolysis of 2',3 ',5'-triacetyl-6-azauridine (I) in aqueous solution (mu = 0.5) and to identify the main intermediates and products of the reaction. Methods. A stability indicating isocratic LC assay was used to study the rate of degradation of 1. A gradient LC assay was used to study the time co urses of the degradants. The products of hydrolysis were isolated by p reparative liquid chromatography and identified by H-1-NMR and CI-MS. The pK(a) value was obtained by potentiometric titration. Results. At 36.8 degrees C, the pH-rate profile of I in water was adequately descr ibed by a four-term rate equation. The intermediates were identified a s the primary and secondary di-acetates, and the primary and secondary mono-acetates. The final product was 6-azauridine. Conclusions. A sim plified kinetic scheme could be used to describe the concentration-tim e profiles of I, the intermediates and the final product.