Accelerated Forced Degradation of Therapeutic Peptides in Levitated Microdroplets
| Autor: | Yuejie Zhao, Yong Liu, Yanyang Hu, David L Logsdon, R. Graham Cooks, Yangjie Li |
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| Rok vydání: | 2020 |
| Předmět: |
Hot Temperature
Drug Compounding Pharmaceutical Science Peptide 02 engineering and technology Octreotide Buserelin 030226 pharmacology & pharmacy Workflow 03 medical and health sciences Hydrolysis 0302 clinical medicine Drug Stability Peptide bond Deamino Arginine Vasopressin Pharmacology (medical) Particle Size Deamidation Ether cleavage Pharmacology chemistry.chemical_classification Aqueous solution Protein Stability Chemistry Organic Chemistry Hydrogen-Ion Concentration 021001 nanoscience & nanotechnology Combinatorial chemistry Kinetics Proteolysis Forced degradation Molecular Medicine Degradation (geology) Leuprolide 0210 nano-technology Biotechnology |
| Zdroj: | Pharmaceutical Research. 37 |
| ISSN: | 1573-904X 0724-8741 |
| DOI: | 10.1007/s11095-020-02868-y |
| Popis: | Forced degradation is critical to probe the stabilities and chemical reactivities of therapeutic peptides. Typically performed in bulk followed by LC-UV or LC-MS analysis, this traditional workflow consists of a reaction/analysis sequence and usually requires half a day to several days to form and measure the desired amounts of degradants. A faster method is needed to study peptide degradation in a shorter time in order to speed up the drug development process.In the new rapid method developed in this study, peptide degradation occurs in levitated aqueous microdroplets using the Leidenfrost effect.This two-minute reaction/analysis workflow allows major degradation pathways of Buserelin, Octreotide, Desmopressin and Leuprorelin to be studied. The reactions include deamidation, disulfide bond cleavage, ether cleavage, peptide bond hydrolysis, and oxidation.The accelerated forced degradation method requires a minimal amount of therapeutic peptide per stress condition, and the appropriate extent of degradation can be readily generated in seconds by adjusting the droplet levitation time. Levitated microdroplets should be applicable in pharmaceutical development to rapidly determine the intrinsic stability of therapeutic peptides and to aid formulation development by screening the effects of excipients on the stability of the peptides. Graphical abstract. |
| Databáze: | OpenAIRE |
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