Characterization and quantification of oxyntomodulin in human and rat plasma using high-resolution accurate mass LC-MS.
BACKGROUND
A thorough understanding of the biological role of oxyntomodulin (OXM) has been limited by the availability of sensitive and specific analytical tools for reliable in vivo characterization. Here, we utilized immunoaffinity capture coupled with high-resolution accurate mass LC-MS detection to quantify OXM and its primary catabolites.


RESULTS
Quantification of intact OXM 1-37 in human and rat plasma occurred in pre- and post-prandial samples. Profiles for the major catabolites were observed allowing kinetic differences to be assessed between species.


CONCLUSIONS
A validated assay in human and rat plasma was obtained for OXM 1-37 and its catabolites, 3-37 and 4-37. The value of full scan high-resolution accurate mass detection without selected reaction monitoring for low-abundance peptide quantification was also demonstrated.
Lilly Research Laboratories, Eli Lilly & Company, Lilly Corporate Center, Indianapolis, IN 46285, USA.
Jennifer M
JM
Cox
Lilly Research Laboratories, Eli Lilly & Company, Lilly Corporate Center, Indianapolis, IN 46285, USA.
Michael J
MJ
Berna
Lilly Research Laboratories, Eli Lilly & Company, Lilly Corporate Center, Indianapolis, IN 46285, USA.
Zhaoyan
Z
Jin
Lilly Research Laboratories, Eli Lilly & Company, Lilly Corporate Center, Indianapolis, IN 46285, USA.
Amy L
AL
Cox
Lilly Research Laboratories, Eli Lilly & Company, Lilly Corporate Center, Indianapolis, IN 46285, USA.
Kyle W
KW
Sloop
Lilly Research Laboratories, Eli Lilly & Company, Lilly Corporate Center, Indianapolis, IN 46285, USA.
Jesus A
JA
Gutierrez
Lilly Research Laboratories, Eli Lilly & Company, Lilly Corporate Center, Indianapolis, IN 46285, USA.
Bradley L
BL
Ackermann
D000818:Animals; D002846:Chromatography, Affinity / Q000379:methods*; D006801:Humans; D057230:Limit of Detection; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D053772:Oxyntomodulin / Q000097:blood*; D051381:Rats; D017207:Rats, Sprague-Dawley
D053772:Oxyntomodulin
catabolites; high-resolution accurate mass MS; immunoaffinity enrichment; orbitrap; oxyntomodulin; quantification; validation