Prediction of Stability in Pharmaceutical Preparations. XIV. The Complete pH Dependent Solvolytic Degradations of an Iodinated Nucleoside, the Antiviral 5-Iodo-2'-deoxyuridine

Abstract

The solvolysis of the antiviral, 5-iodo-2[image]-deoxyuridine (IDU) is catalyzed by hydrogen ions and solvent, in the acetate and low pH phosphate buffer regions, and by hy-droxyl ions and solvent, in the borate buffer and high pH alkaline region. The solvolysis of IDU is first-order with respect to IDU over the pH range of 3. 9 to 12. 0. The Arrhenius parameters at different pH values varied. These parameters were evaluated at specific pH values. The general procedure for the prediction of stability of IDU an any pH value was discussed. In the alkaline region the proposed mechanism involves 2 routes: the production of uracil through the formation of the intermediate deoxyuridine as the minor route and the formation of 5-hydroxy -2[image] -deoxyuridine which degrades further as the major route.