3'-Azido-3'-deoxy-5'-O-isonicotinoylthymidine: a novel antiretroviral analog of zidovudine. II. Stability in aqueous media and experimental and theoretical ionization constants

Nucleosides Nucleotides Nucleic Acids. 2003 Sep;22(9):1789-803. doi: 10.1081/NCN-120023273.

Abstract

Degradation of 3'-azido-3'-deoxy-5'-O-isonicotinoylthymidine (AZT-Iso), an antiretroviral derivative of zidovudine, was investigated in buffer pH 7.4, mu = 300 mOsm at 37, 50 and 60 degrees C, and in water (pH 6.6, 37 degrees C), giving zidovudine (AZT) and isonicotinic acid (INA) as products. The rate constants were determined by reversed-phase HPLC showing pseudo-first-order kinetics related to the residual amount of AZT-Iso. In this way, the studied compound was demonstrated to be 153 times more stable in water than in buffer solution at 37 degrees C. The analytical method was conveniently validated demonstrating to be a rapid and accurate stability-indicating technique. In addition, experimental and theoretical values of pKa were determined.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / chemistry*
  • Chromatography, High Pressure Liquid / methods
  • Isonicotinic Acids / chemistry
  • Kinetics
  • Molecular Structure
  • Water / chemistry
  • Zidovudine / analogs & derivatives
  • Zidovudine / chemistry*

Substances

  • 3'-azido-3'-deoxy-5'-O-isonicotinoylthymidine
  • Anti-HIV Agents
  • Isonicotinic Acids
  • Water
  • Zidovudine