Isotope-Edited Infrared Spectroscopy for Efficient Discrimination between Pharmaceutical Salts and Cocrystals

Mol Pharm. 2017 Jul 3;14(7):2350-2358. doi: 10.1021/acs.molpharmaceut.7b00226. Epub 2017 May 26.

Abstract

Isotope-edited infrared spectroscopy using carboxylic acids selectively labeled with 13C is proposed herein for the efficient discrimination of pharmaceutical salts and cocrystals, whereby proton-transfer probe vibrations are highlighted by isotope shifts. This new technique can accurately discriminate even a confusing salt from a cocrystal for the traditional method, highlighting the diagnostic peaks. In addition, the established technique also provided the OH in-plane bending vibrations corresponding to intermolecular hydrogen bonding at the carbonyl oxygens of the cocrystals. The technique will accelerate the discrimination, which is a critical process in cocrystal development.

Keywords: cocrystal; infrared spectroscopy; isotope shift and carboxylic acid; salt.

MeSH terms

  • Carboxylic Acids / chemistry
  • Crystallization
  • Hydrogen Bonding
  • Molecular Structure
  • Salts / chemistry*
  • Spectrophotometry, Infrared / methods*

Substances

  • Carboxylic Acids
  • Salts