Hydrolysis of the prodrug, 2',3',5'-triacetyl-6-azauridine

Pharm Res. 1995 Sep;12(9):1361-70. doi: 10.1023/a:1016238110533.

Abstract

Purpose: The purposes were to study the kinetics of hydrolysis of 2',3',5'-triacetyl-6-azauridine (1) 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 courses of the degradants. The products of hydrolysis were isolated by preparative liquid chromatography and identified by 1H-NMR and CI-MS. The pKa value was obtained by potentiometric titration.

Results: At 36.8 degrees C, the pH-rate profile of 1 in water was adequately described by a four-term rate equation. The intermediates were identified as the primary and secondary di-acetates, and the primary and secondary mono-acetates. The final product was 6-azauridine.

Conclusions: A simplified kinetic scheme could be used to describe the concentration-time profiles of 1, the intermediates and the final product.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Azauridine / analogs & derivatives*
  • Azauridine / chemistry
  • Drug Stability
  • Hydrogen-Ion Concentration
  • Hydrolysis
  • In Vitro Techniques
  • Kinetics
  • Models, Chemical
  • Molecular Structure
  • Prodrugs / chemistry*
  • Solutions
  • Temperature
  • Thermodynamics
  • Water

Substances

  • Prodrugs
  • Solutions
  • Water
  • Azauridine
  • azaribine