Tirzepatide

Tirzepatide is a synthetic 39-amino-acid peptide engineered for dual activity at the GIP and GLP-1 receptors. The backbone carries three pharmacology-defining modifications:

• Two α-aminoisobutyric acid (Aib) residues at positions 2 and 13 that block DPP-4 cleavage and stabilize the backbone.
• Lys20 lipidation — the side-chain amine is conjugated through a γGlu-γGlu spacer to a C20 fatty diacid (eicosanedioic acid), which supports reversible albumin binding and the once-weekly dosing window described in the published clinical literature.
• C-terminal extension — the sequence ends in a Gly-rich tail (...AGGPSSGAPPPS) that contributes to receptor selectivity.

Molecular formula C225H348N48O68; average molecular weight approximately 4813.45 Da. CAS 2023788-19-2.

Tirzepatide is assembled by SPPS and site-selectively acylated at Lys20 with the γGlu-γGlu-C20 linker. The molecule is long enough, and the linker chemistry sensitive enough, that several impurity classes are essentially expected:

• Backbone deletions and truncations — over 39 cycles, even small per-cycle inefficiency compounds.
• Aib-position diastereomers at positions 2 and 13.
• Linker positional isomers — the lipid is intended for Lys20 only; competing acylation at any other lysine or the N-terminus produces a molecule with the same intact mass but different pharmacology. Only peptide mapping can resolve this.
• Free C20-diacid linker from incomplete coupling.
• Oxidized methionine and tryptophan from storage.
• Aggregates and high-molecular-weight species from lipid-driven self-assembly.

The verification panel is built around the fact that intact-mass MS cannot distinguish linker positional isomers:

• RP-HPLC purity with wide-pore C4 column (TFA / MeCN, UV 214 nm)
• LC-HRMS identity (ESI-Q-TOF, deconvoluted average mass)
• Tryptic peptide mapping with LC-MS/MS to confirm full sequence and Lys20 lipid attachment
• Quantitative HPLC vs reference standard for content
• SEC-HPLC for aggregates

Method conditions are reported in full on the Certificate of Analysis. See characterizing a peptide for what each method measures.

Co-activates GIP and GLP-1 receptors. The pharmacology is detailed in the discovery paper (Coskun et al., 2018) and subsequent reviews; CertikLabs reports only what is needed to verify the chemistry of a supplied sample.

Primary sources:

• Coskun T. et al., LY3298176, a novel dual GIP and GLP-1 receptor agonist.(PMID 30293770)
• Willard F.S. et al., Tirzepatide: pharmacology of a dual GIP and GLP-1 receptor agonist.(PMID 35551238)

CertikLabs does not publish dosing, administration routes, or clinical recommendations for tirzepatide.

Like other lipidated peptides, tirzepatide is sensitive to surface adsorption, aggregation, and oxidation in solution. Lyophilized powder is generally stable refrigerated and protected from light; once reconstituted, container choice, pH, and oxygen exposure all materially affect stability and any working solution should be re-verified analytically.