Impurity Monitoring Of GLP-1 Therapeutic Peptide Retatrutide Using A 2D-LC/TOF System

Retatrutide, an emerging triple GLP1/GIP/glucagon agonist, presents an impurity profile that tests the limits of one-dimensional LC. TFA is the familiar choice in regulated QA/QC settings for good reason: in a head-to-head UV comparison, it baseline-separated three impurity peaks from the main peak, while formic acid let one co-elute. The catch is ion suppression in MS. This poster from Li Gu, Linfeng Wu, and Guannan Li of Agilent Technologies shows how multiple heart-cutting 2D-LC, coupled to an accurate mass TOF system, keeps the TFA separation in the first dimension while moving to formic acid conditions for detection. The impurity data, including proposed identities for the observed mass shifts, offer a concrete look at the approach in practice.

Access the full poster to see the cuts, spectra, and method parameters.