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Buserelin: a solid state peptide degradation kinetic and mechanistic study

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Abstract
Buserelin is a GnRH agonist peptide drug, comprising a nine amino acid sequence (pGlu-His-Trp-Ser-Tyr-D-Ser(tBu)-Leu-Arg-Pro-NH-Et) and most commonly known for its application in hormone dependent cancer therapy, e.g. prostate cancer. In order to evaluate its hot-melt extrusion (HME) capabilities, buserelin powder in its solid state was exposed to elevated temperatures for different time periods. A stability indicating UPLC-PDA method was used for quantification of buserelin and the formed degradation products. Different solid state kinetic degradation models were statistically evaluated of which the Ginstling-Brounshtein model fitted the data best. Mass spectrometric analysis of the buserelin-related degradants demonstrated three different degradation mechanisms (Fig. 1). First, β-elimination of the hydroxyl moiety at the serine residue, followed by fragmentation into an amide (pGlu-His-Trp-NH2) and pyruvoyl (pyruvoyl-Tyr-D-Ser (tBu)-Leu-Arg-Pro-NHEt) peptide fragment was observed. Degradant pGlu-His-Trp-Ser-Tyr-NH2 is believed to be formed in a similar way. Secondly, backbone hydrolysis was observed yielding pGlu-His-Trp and Tyr-Ser(tBu)-Leu-Arg-Pro-NH-Et peptide fragments. Moreover, the presence of Ala-Tyr-Ser(tBu)-Leu-Arg-Pro-NH-Et is explained by subsequent hydrolysis of Trp-Ser peptide bond and conversion of the serine moiety to an alanine moiety. Finally, isomerisation of aforementioned peptide fragments and buserelin itself was also observed [1].
Keywords
peptide, buserelin, mass spectrometry, dry heat, degradation

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MLA
D’Hondt, Matthias et al. “Buserelin: a Solid State Peptide Degradation Kinetic and Mechanistic Study.” Belgian-Dutch Biopharmaceutical Society, Autumn Meeting, Abstracts. 2013. Print.
APA
D’Hondt, M., Peng, C.-Y., Hoffmann, R., & De Spiegeleer, B. (2013). Buserelin: a solid state peptide degradation kinetic and mechanistic study. Belgian-Dutch Biopharmaceutical Society, Autumn meeting, Abstracts. Presented at the 2013 Autumn meeting of the Belgian-Dutch Biopharmaceutical Society.
Chicago author-date
D’Hondt, Matthias, Chien-Yu Peng, Ralf Hoffmann, and Bart De Spiegeleer. 2013. “Buserelin: a Solid State Peptide Degradation Kinetic and Mechanistic Study.” In Belgian-Dutch Biopharmaceutical Society, Autumn Meeting, Abstracts.
Chicago author-date (all authors)
D’Hondt, Matthias, Chien-Yu Peng, Ralf Hoffmann, and Bart De Spiegeleer. 2013. “Buserelin: a Solid State Peptide Degradation Kinetic and Mechanistic Study.” In Belgian-Dutch Biopharmaceutical Society, Autumn Meeting, Abstracts.
Vancouver
1.
D’Hondt M, Peng C-Y, Hoffmann R, De Spiegeleer B. Buserelin: a solid state peptide degradation kinetic and mechanistic study. Belgian-Dutch Biopharmaceutical Society, Autumn meeting, Abstracts. 2013.
IEEE
[1]
M. D’Hondt, C.-Y. Peng, R. Hoffmann, and B. De Spiegeleer, “Buserelin: a solid state peptide degradation kinetic and mechanistic study,” in Belgian-Dutch Biopharmaceutical Society, Autumn meeting, Abstracts, Ghent, 2013.
@inproceedings{4211639,
  abstract     = {Buserelin is a GnRH agonist peptide drug, comprising a nine amino acid sequence (pGlu-His-Trp-Ser-Tyr-D-Ser(tBu)-Leu-Arg-Pro-NH-Et) and most commonly known for its application in hormone dependent cancer therapy, e.g. prostate cancer. In order to evaluate its hot-melt extrusion (HME) capabilities, buserelin powder in its solid state was exposed to elevated temperatures for different time periods. A stability indicating UPLC-PDA method was used for quantification of buserelin and the formed degradation products. Different solid state kinetic degradation models were statistically evaluated of which the Ginstling-Brounshtein model fitted the data best.
Mass spectrometric analysis of the buserelin-related degradants demonstrated three different degradation mechanisms (Fig. 1). First, β-elimination of the hydroxyl moiety at the serine residue, followed by fragmentation into an amide (pGlu-His-Trp-NH2) and pyruvoyl (pyruvoyl-Tyr-D-Ser (tBu)-Leu-Arg-Pro-NHEt) peptide fragment was observed. Degradant pGlu-His-Trp-Ser-Tyr-NH2 is believed to be formed in a similar way. Secondly, backbone hydrolysis was observed yielding pGlu-His-Trp and Tyr-Ser(tBu)-Leu-Arg-Pro-NH-Et peptide fragments. Moreover, the presence of Ala-Tyr-Ser(tBu)-Leu-Arg-Pro-NH-Et is explained by subsequent hydrolysis of Trp-Ser peptide bond and conversion of the serine moiety to an alanine moiety. Finally, isomerisation of aforementioned peptide fragments and buserelin itself was also observed [1].},
  author       = {D'Hondt, Matthias and Peng, Chien-Yu and Hoffmann, Ralf and De Spiegeleer, Bart},
  booktitle    = {Belgian-Dutch Biopharmaceutical Society, Autumn meeting, Abstracts},
  keywords     = {peptide,buserelin,mass spectrometry,dry heat,degradation},
  language     = {eng},
  location     = {Ghent},
  title        = {Buserelin: a solid state peptide degradation kinetic and mechanistic study},
  year         = {2013},
}