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Updated: Aug 14, 2026

Determination of the Gas-phase Acidities of Oligopeptides
Published on: June 24, 2013
Solid state chemical instability of an asparaginyl residue in a model hexapeptide
1Department of Pharmaceutical Chemistry, University of Kansas, Lawrence 66045.
Abstract:
The chemical stability of an Asn-hexapeptide (Val-Tyr-Pro-Asn-Gly-Ala) in lyophilized formulations was evaluated as a function of the pH of the bulk solution, temperature, and residual moisture content in a factorial study. Degradation pathways and product distribution in solid state were determined and characterized. It was shown in this study that the pH of the starting solution had a significant effect on the rate of deamidation and product distribution. In general, better stability for the Asn-hexapeptide was achieved at a slightly acidic pH range (3-5) in the solid state. The effects of residual moisture level and temperature on peptide stability proved to be less significant. A statistically significant two-factor interaction indicated that the pH of formulation solution determined the extent to which the peptide stability depends on moisture level and temperature. In general, the degradation of the Asn-hexapeptide in the solid state was similar to that observed in solution, except for the observation that no isoAsp-hexapeptide was detected at pH 5.0 in the solid state, whereas this was the major degradation product in solution.
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