Mass spec workflow maps metabolic soft spots of insulin degludec, linaclotide

The wire

1. 01Researchers in Drug Metabolism and Disposition identified 95 insulin degludec metabolites, 20 insulin glargine metabolites in human serum, and 13 linaclotide metabolites across liver and intestinal S9 incubations.
2. 02Disulfide-constrained peptide drugs resist enzymatic cleavage and suppress b/y-ion formation, leaving developers with incomplete metabolite maps; the authors say reduction and alkylation remove that analytical complexity.
3. 03The work is in vitro across biological matrices only, and the authors present it as a transferable analytical strategy rather than new clinical data on any of the three drugs.

From the source

Rapid and comprehensive identification of the metabolic soft spots of peptide drugs with highly cross-linked disulfide bonds by integrating established proteomic workflow with a product ion filtering strategy

Drug metabolism and disposition: the biological fate of chemicals · 2026 Jul 17 · Ye X, Qin H, Zhang W et al.