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. 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.
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Authors | Yan Wang, Ying Qu, Chris L Bellows, John S Ahn, Jennifer L Burkey, Steven W Taylor |
Journal | Bioanalysis
(Bioanalysis)
Vol. 4
Issue 17
Pg. 2141-52
(Sep 2012)
ISSN: 1757-6199 [Electronic] England |
PMID | 23013396
(Publication Type: Journal Article)
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Chemical References |
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Topics |
- Animals
- Chromatography, Liquid
(methods)
- Dogs
- Humans
- Peptides
(blood, pharmacokinetics)
- Rats
- Solid Phase Extraction
(methods)
- Tandem Mass Spectrometry
(methods)
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