ArticlePharmaceutical research2020
Accelerated Forced Degradation of Therapeutic Peptides in Levitated Microdroplets.
Article in Pharmaceutical research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 15 citations in OpenAlex.
- Fragment correlation mass spectrometry: Determining the structures of biopolymers in a complex mixture without isolating individual components.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Silica particles convert thiol-containing molecules to disulfides.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Glass surface as strong base, 'green' heterogeneous catalyst and degradation reagent.Chemical science · 2021Article
- Recent advances in analytical techniques for high throughput experimentation.Analytical science advances · 2021Review
- Microdroplet Ultrafast Reactions Speed Antibody Characterization.Analytical chemistry · 2021Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeForced 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.
methodsIn the new rapid method developed in this study, peptide degradation occurs in levitated aqueous microdroplets using the Leidenfrost effect.
resultsThis 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.
conclusionsThe 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.
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Registered trials
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