Solid-state stability studies of crystal form of tebipenem

Drug Dev Ind Pharm. 2016;42(2):238-44. doi: 10.3109/03639045.2015.1044902. Epub 2015 Jun 5.

Abstract

The aim of this study was to determine the kinetic and thermodynamic parameters of tebipenem degradation in the solid state. The process was analyzed based on the results obtained by a high performance liquid chromatography (HPLC) method using ultraviolet diode-array detector (DAD)/electrospray ionization tandem mass spectrometry (Q-TOF-MS/MS), Fourier transform infrared spectroscopy (FT-IR) and Raman spectroscopic (RS) studies. In dry air, the degradation of tebipenem was a first-order reaction depending on the substrate concentration while at an increased relative air humidity tebipenem was degraded according to the kinetic model of autocatalysis. The thermodynamic parameters: energy of activation (Ea), enthalpy (ΔH(≠a)) and entropy (ΔS(≠a)) of tebipenem degradation were calculated. Following a spectroscopic analysis of degraded samples of tebipenem, a cleavage of the β-lactam bond was proposed as the main degradation pathway, next confirmation using HPLC-Q-TOF-MS/MS method.

Keywords: Kinetic and thermodynamic analysis; solid-state stability; tebipenem.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemistry*
  • Carbapenems / chemistry*
  • Chromatography, High Pressure Liquid / methods*
  • Crystallization
  • Drug Stability
  • Humidity
  • Kinetics
  • Spectrometry, Mass, Electrospray Ionization / methods
  • Spectroscopy, Fourier Transform Infrared
  • Tandem Mass Spectrometry / methods*
  • Thermodynamics

Substances

  • Anti-Bacterial Agents
  • Carbapenems
  • tebipenem