Mechanistic insight into the oxazoline decomposition of DFC-M, a synthetic intermediate of florfenicol

J Pharm Biomed Anal. 2019 Sep 10:174:235-241. doi: 10.1016/j.jpba.2019.05.009. Epub 2019 May 31.

Abstract

2-(dichloromethyl)-5[4-(methylsulfonyl)-phenyl]-4-(fluoromethyl)-oxazoline (DFC-M, 1) is a key oxazoline-containing intermediate in commercial process for the synthesis of Florfenicol (3), a marketed broad spectrum veterinary antibiotic. DFC-M was not stable in solution due to the presence of oxazoline moiety, which provided further hindrance for analytical sample preparation and HPLC analysis. Hence, the mechanistic study on the in-solution degradation of DFC-M was carried out via online and offline UPLC-HR-ESI-MS as well as in-situ NMR, and the degradation pathways were proposed. This mechanistic information, together with the follow-up solution stability study, provided crucial information regarding the solution handling and mobile phase selection for DFC-M analysis during commercial processing.

Keywords: Florfenicol; Florfenicol amine; NMR; On-column decomposition; Oxazoline; UHPLC-HR-ESI-MS.

MeSH terms

  • Chromatography, High Pressure Liquid
  • Chromatography, Liquid
  • Drug Residues / analysis
  • Drug Stability
  • Hydrolysis
  • Indicators and Reagents
  • Kinetics
  • Magnetic Resonance Spectroscopy
  • Oxazoles / analysis*
  • Solvents
  • Spectrometry, Mass, Electrospray Ionization
  • Tandem Mass Spectrometry
  • Thiamphenicol / analogs & derivatives*
  • Thiamphenicol / analysis
  • Thiamphenicol / metabolism

Substances

  • Indicators and Reagents
  • Oxazoles
  • Solvents
  • florfenicol
  • Thiamphenicol