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Tirzepatide vs Semaglutide COA: How to Compare Them Side by Side

A direct comparison of what a good tirzepatide COA and semaglutide COA should show — purity thresholds, related substances, identity confirmation, and contaminant panels.

July 7, 2026
Last reviewed

# Tirzepatide vs Semaglutide COA: How to Compare Them Side by Side

Tirzepatide and semaglutide are the two most-tested GLP-1 class peptides at independent labs today. Their COAs look superficially similar. The details differ in ways that matter.

Structural differences that drive testing choices

Semaglutide is a 31-residue GLP-1 analog with a C18 fatty di-acid conjugate at Lys26 via a γGlu-2xOEG linker. Tirzepatide is a 39-residue dual GIP/GLP-1 agonist with a C20 fatty di-acid at Lys20 via a γGlu-2xAEEA linker. Both are heavily engineered lipopeptides; both share analytical challenges around lipid-driven peak broadening. The methods overlap, but the impurity fingerprints are distinct.

Purity thresholds

Both peptides typically report ≥98% HPLC purity from a competent SPPS route. A COA reporting 95% for either should be treated with caution.

  • Semaglutide — most common flagged impurities: des-lipid backbone, Asp8 aspartimide product, Met14 oxidation.
  • Tirzepatide — most common: des-C20 lipid, N-terminal deletions, aminoisobutyric acid (Aib) coupling failures at positions 2 and 13.

A COA that reports only "total impurities" without naming these peaks is not doing peptide-specific work.

Identity confirmation

  • Semaglutide theoretical mass: approximately 4113.58 Da monoisotopic
  • Tirzepatide theoretical mass: approximately 4813.53 Da monoisotopic

Both should be confirmed by LC-MS deconvolution within a few ppm. Des-lipid analogs and near-neighbor deletions pass a purity check but fail a mass check.

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Method notes

Semaglutide is comfortable on a standard C18 lipopeptide-friendly method. Tirzepatide, because of Aib residues and the different linker chemistry, benefits from a slightly steeper gradient near the elution window and higher column temperature. Labs running both regularly maintain two dedicated methods.

Contaminant panels

Both peptides for research injectable use should carry ICP-MS heavy metals, GC-MS residual solvents, LAL endotoxin in EU/mg, and Karl Fischer water content. Semaglutide is more likely to see residual acetate; tirzepatide more likely to see residual TFA.

Comparing two supplier COAs

Ask five questions:

  1. Is main peak purity supported by an itemized related substances table?
  2. Is LC-MS identity confirmed with observed mass and delta ppm?
  3. Are peptide-specific impurities named (des-lipid, aspartimide, Aib coupling failures)?
  4. Are contaminant panels included, or only mentioned in the specification section?
  5. Is the method disclosed in enough detail that a third lab could reproduce it?

A COA that answers yes to all five is credible. A COA that dodges any of the five is a signal to send the material out for independent testing.

Where independent testing changes the decision

Both peptides move in large enough volumes that supplier lot-to-lot variance is real. Independent testing on a rolling basis — one lot per shipment, or one out of every three — is the cheapest insurance against a bad batch making it into inventory.

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