Simultaneous quantification of davalintide, a novel amylin-mimetic peptide, and its active metabolite in beagle and rat plasma by online SPE and LC-MS/MS
| Autor: | Chris L Bellows, Jennifer L Burkey, Yan Wang, Steven W. Taylor, John S. Ahn, Ying Qu |
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| Rok vydání: | 2012 |
| Předmět: |
Metabolite
Clinical Biochemistry Amylin Peptide Analytical Chemistry chemistry.chemical_compound Dogs Pharmacokinetics In vivo Tandem Mass Spectrometry Immunochemistry Animals Humans General Pharmacology Toxicology and Pharmaceutics Active metabolite chemistry.chemical_classification Chromatography biology Solid Phase Extraction General Medicine Rats Medical Laboratory Technology chemistry biology.protein Antibody Peptides Chromatography Liquid |
| Zdroj: | Bioanalysis. 4(17) |
| ISSN: | 1757-6199 |
| Popis: | Background: Davalintide, an investigational therapeutic peptide for the treatment of obesity, is rapidly metabolized by enzymatic cleavage of its N-terminal lysine residue to produce an active des-Lys metabolite in vivo. While a sensitive ELISA assay is available, it is unable to distinguish davalintide from its metabolite. Consequently, we developed an online SPE–LC–MS/MS method for simultaneous quantification of the drug and its active metabolite in beagle and rat plasma samples and compared the resulting pharmacokinetic profiles with those determined by ELISA. Results: The total concentration of active drug measured by ELISA correlated well with the total concentration of davalintide and its metabolite using online SPE–LC–MS/MS. Conclusion: The technique is a viable alternative to immunochemistry-based methods for peptide quantitation in terms of sensitivity, reproducibility and specificity, and importantly, does not require developing antibody-based reagents. |
| Databáze: | OpenAIRE |
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