In-vitro metabolite identification for MEDI7219, an oral GLP-1 analog, using LC-MS/MS with CID and EAD approaches.

ABSTRACT:

Aim

Oral peptide therapeutics typically have short half-lives due to rapid degradation by digestive enzymes. Systematic peptide engineering and formulation optimization led to the development of a clinical candidate MEDI7219, an orally bioavailable glucagon-like peptide 1 (GLP-1) peptide, with greater stability than wild-type GLP-1 or semaglutide:~60% of MEDI7219 remained intact after 2 h in vitro incubation with simulated intestinal fluid. This study further investigates proteolytic stability by elucidating biotransformation products of MEDI7219 using liquid chromatography-mass spectrometry (LC-MS) methods.

Method

Peptide metabolism was assessed using in vitro pancreatin assay followed by analysis utilizing liquid chromatography coupled with tandem mass spectrometry (LC-MS/

SUBMITTER: Liu K 

PROVIDER: S-EPMC12369624 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature