IRBM used liquid chromatography-high resolution mass spectrometry to explore different methods for the study of catabolism (breakdown) which is a key driver in the design of more stable peptides.This is challenging to do analytically in a way that captures the highly heterogeneous products generated from catabolism and provide a full picture of what is happening. The art of it is having the right protein precipitation (PP) and solid-phase extraction (SPE) protocols. The paper gives insights on selecting optimal PP & SPE extraction conditions for the study of peptide catabolism, based on examining four model peptides representative of different structural classes: somatostatin, GLP‐2, human insulin and liraglutide.