title: 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.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Amylin Pharmaceuticals, Inc, 9360 Towne Centre Drive, San Diego, CA 92121, USA. yan.wang555@gmail.com
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Ying
authors.initials: Y
authors.lastname: Qu
authors.forename: Chris L
authors.initials: CL
authors.lastname: Bellows
authors.forename: John S
authors.initials: JS
authors.lastname: Ahn
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Burkey
authors.forename: Steven W
authors.initials: SW
authors.lastname: Taylor
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods*; D004285:Dogs; D006801:Humans; D010455:Peptides / Q000097:blood* / Q000493:pharmacokinetics; D051381:Rats; D052616:Solid Phase Extraction / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D010455:Peptides; C553163:davalintide