Preliminary studies of the physical stability of a glucagon-like peptide-1 derivate in the presence of metal ions

Eur J Pharm Biopharm. 2007 Jun;66(3):366-71. doi: 10.1016/j.ejpb.2006.11.019. Epub 2006 Dec 1.

Abstract

The physical stability and the secondary structure of a glucagon-like peptide-1 derivative were investigated in the presence of the metal ions Al(3+), Zn(2+), Mg(2+), and K(+), known as possible leachables from container-closure systems. Metal ions were investigated in concentrations of 0-50 ppm. Test solutions of the peptide were exposed to elevated temperature (25 degrees C) and rotation (37 degrees C) for up to 4 weeks. The samples were examined by nephelometry, thioflavine T fluorescence, and Fourier-transform infrared spectroscopy. Readily prepared test solutions were examined by tryptophan fluorescence. The stability profiles were unchanged after addition of Mg(2+) and K(+) in 0-50 ppm concentrations. However, a concentration-dependent increase in thioflavine intensities was observed after addition of Al(3+) and Zn(2+). The destabilising effect of Al(3+) and Zn(2+) was furthermore confirmed by FTIR as the secondary structure of the peptide changed from predominantly alpha-helix to a higher beta-sheet content. Additionally Al(3+) changed the secondary structure of the peptide using Trp fluorescence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aluminum / pharmacology
  • Drug Stability
  • Glucagon-Like Peptide 1 / analogs & derivatives
  • Glucagon-Like Peptide 1 / chemistry*
  • Magnesium / pharmacology
  • Metals / pharmacology*
  • Nephelometry and Turbidimetry
  • Potassium / pharmacology
  • Spectroscopy, Fourier Transform Infrared
  • Zinc / pharmacology

Substances

  • Metals
  • Glucagon-Like Peptide 1
  • Aluminum
  • Magnesium
  • Zinc
  • Potassium