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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.

AbstractBACKGROUND:
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.
AuthorsYan Wang, Ying Qu, Chris L Bellows, John S Ahn, Jennifer L Burkey, Steven W Taylor
JournalBioanalysis (Bioanalysis) Vol. 4 Issue 17 Pg. 2141-52 (Sep 2012) ISSN: 1757-6199 [Electronic] England
PMID23013396 (Publication Type: Journal Article)
Chemical References
  • Peptides
  • davalintide
Topics
  • Animals
  • Chromatography, Liquid (methods)
  • Dogs
  • Humans
  • Peptides (blood, pharmacokinetics)
  • Rats
  • Solid Phase Extraction (methods)
  • Tandem Mass Spectrometry (methods)

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