Solid-state stability studies of cholecystokinin (CCK-4) peptide under nonisothermal conditions using thermal analysis, chromatography and mass spectrometry

The solid-state stability of cholecystokinin (CCK-4) peptide under nonisothermal conditions was studied by differential scanning calorimetry (DSC), chromatography and mass spectrometry, identifying and schematizing the degradation products. To model the degradation mechanism of the peptide using the...

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Veröffentlicht in:European journal of pharmaceutical sciences 2010-02, Vol.39 (4), p.263-271
Hauptverfasser: Oliva, Alexis, Ashen, David Sánchez, Salmona, Mario, Fariña, José B., Llabrés, Matías
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container_end_page 271
container_issue 4
container_start_page 263
container_title European journal of pharmaceutical sciences
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creator Oliva, Alexis
Ashen, David Sánchez
Salmona, Mario
Fariña, José B.
Llabrés, Matías
description The solid-state stability of cholecystokinin (CCK-4) peptide under nonisothermal conditions was studied by differential scanning calorimetry (DSC), chromatography and mass spectrometry, identifying and schematizing the degradation products. To model the degradation mechanism of the peptide using the combined Kissinger and direct-differential methods, the observed degradation process was characterized by decomposition temperature ( T m), reacted fraction ( α m), activation energy ( E a), and pre-exponential factor ( A). Results obtained by the two calculation methods were similar. The cleavage reaction on both N- and C-terminal sides of aspartic acid was the principal degradation pathway, although the reaction can occur consecutively and/or in parallel. Therefore to determine the relative importance of the different degradation pathways, a system of differential equations relevant to each degradation reaction was analysed using the R ® statistical program. The results obtained show that the consecutive reaction was the less plausible, whereas a slightly better fit was obtained for the reaction with both processes than for the in-parallel reaction. In this situation, the F-test was applied to discriminate between the models, indicating that the simpler model is the most probable. In conclusion, the results demonstrate for the first time that, in solid-state, n − 1 cleavage occurs in parallel to n + 1 cleavage at aspartic acid residues and not consecutively.
doi_str_mv 10.1016/j.ejps.2009.12.010
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Pharmaceutical industry</topic><topic>Pharmacology. 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subjects Biological and medical sciences
Calorimetry, Differential Scanning - methods
Chromatography, High Pressure Liquid - methods
DSC
General pharmacology
Hot Temperature
Mass Spectrometry - methods
Medical sciences
Nonisothermal kinetic analysis
Peptide cleavage
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Protein Denaturation
Protein Stability
Solid-state stability
Solubility
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization - methods
Tetragastrin - analysis
Tetragastrin - chemistry
Tetragastrin - pharmacokinetics
title Solid-state stability studies of cholecystokinin (CCK-4) peptide under nonisothermal conditions using thermal analysis, chromatography and mass spectrometry
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