Preliminary studies of the physical stability of a glucagon-like peptide-1 derivate in the presence of metal ions.
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.
Christensen
Stina
S
Novo Nordisk A/S, Gentofte, Denmark.
Moeller
Eva Horn
EH
Bonde
Claude
C
Lilleoere
Anne-Mette
AM
D000535:Aluminum / Q000494:pharmacology; D004355:Drug Stability; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives / Q000737:chemistry*; D008274:Magnesium / Q000494:pharmacology; D008670:Metals / Q000494:pharmacology*; D009391:Nephelometry and Turbidimetry; D011188:Potassium / Q000494:pharmacology; D017550:Spectroscopy, Fourier Transform Infrared; D015032:Zinc / Q000494:pharmacology
D008670:Metals; D052216:Glucagon-Like Peptide 1; D000535:Aluminum; D008274:Magnesium; D015032:Zinc; D011188:Potassium