pH-Dependent stability of azithromycin in aqueous solution and structure identification of two new degradation products

J Pharm Biomed Anal. 2018 Sep 5:158:47-53. doi: 10.1016/j.jpba.2018.05.042. Epub 2018 May 28.

Abstract

The degradation profile of azithromycin in buffered solutions was investigated using HPLC and found to be pH dependent in the range of 6.0-7.2. Desosaminylazitromycin, derived from hydrolytic loss of cladinose of the parent molecule, was the major degradation product at pH 6.0 but its amount progressively decreased moving toward pH 7.2. Two additional unreported degradation products were also observed and their structures were fully elucidated by MS- and NMR-spectroscopy to be associated with opening of the macrocyclic lactone ring.

Keywords: Aqueous solution; Azithromycin; HPLC analysis; Lactone opening; pH-Dependent degradation.

MeSH terms

  • Anti-Bacterial Agents / chemistry*
  • Azithromycin / chemistry*
  • Chromatography, High Pressure Liquid / instrumentation
  • Chromatography, High Pressure Liquid / methods
  • Drug Stability*
  • Hydrogen-Ion Concentration
  • Hydrolysis
  • Magnetic Resonance Spectroscopy / instrumentation
  • Magnetic Resonance Spectroscopy / methods
  • Molecular Structure
  • Solutions
  • Temperature
  • Water / chemistry

Substances

  • Anti-Bacterial Agents
  • Solutions
  • Water
  • Azithromycin