Accepted answer
It is an identity claim, and it is the one place where a single word on a COA changes the regulatory status of the material and the amount of drug in the vial at the same time.
The regulatory half
A 503A pharmacy may compound from a bulk drug substance if that substance is the subject of a USP or NF monograph, is a component of an FDA-approved drug, or appears on the 503A bulks list. For semaglutide, the doorway everyone relies on is the second one — it is a component of approved products. But that doorway is form-specific: the approved products contain semaglutide, not a sodium salt of semaglutide. A salt is a different active moiety and therefore not the component of the approved drug. FDA has said explicitly that it received reports of compounders using salt forms, that salt forms are different active ingredients from what is in the approved products, and that it is not aware of any basis for compounding with them. That statement is why the word matters: a COA saying "semaglutide sodium" is documentary evidence that the material does not qualify through the doorway the compounder is relying on.
The same logic applies to tirzepatide, where no salt form appears in any approved product either.
The measurable half
Whatever you think of the regulatory argument, salt form changes mass, and mass is what gets weighed into a vial. Semaglutide is a lipidated 31-residue peptide with a molecular weight of roughly 4,113 Da, and it carries several acidic side chains plus the C18 diacid linker, so as a lyophilised powder it exists with counterions and with substantial bound water. That means gross powder mass and peptide mass are not the same number, and the gap is not small.
Work an example. Suppose a compounder weighs 100 mg of powder intending 100 mg of peptide, and the COA reports:
- HPLC purity (area %): 99.2%
- Water content by Karl Fischer: 6.1%
- Acetate content: 4.8%
Net peptide content is roughly 100 mg × 0.992 × (1 − 0.061 − 0.048) = 100 × 0.992 × 0.891 = 88.4 mg. So the vial labelled 100 mg contains about 88 mg of peptide — an 11.6% shortfall — and every one of those numbers on the COA was excellent. Nothing was faked. HPLC purity in area percent tells you what fraction of the chromatographically detected material is your target; it says nothing whatsoever about how much of the powder is peptide rather than water and counterion.
Now swap the counterion. A sodium salt has a different counterion stoichiometry and different hygroscopicity from an acetate or trifluoroacetate salt, so the same nominal weighing yields a different peptide mass again. Unless the person filling the vial is correcting for net peptide content on that specific lot, the label strength is a guess with a systematic bias.
Why a supplier would list a salt at all
Three legitimate-ish reasons and one bad one:
- It is genuinely what came off the process. Peptides are typically purified by reverse-phase HPLC with an acidic modifier and lyophilised, and they come out as a salt of whatever acid was in the mobile phase. Trifluoroacetate is the classic case and requires an explicit ion-exchange step to convert. So "acetate" on a COA is often just honest process reporting.
- Stability or handling. A given salt may be less hygroscopic or easier to lyophilise consistently.
- Different intended market. A supplier selling reference or research material has no reason to care which form a US compounder needs.
- Deliberate ambiguity. The bad one. Naming the salt in the small print while marketing the base lets a seller answer both questions truthfully to different audiences.
What to actually ask for
Four items, and if any is missing the document is decorative: the exact substance name including salt form; net peptide content or content assay expressed as mg peptide per mg powder; water content by Karl Fischer; and residual counterion content, with trifluoroacetate quantified specifically if the process used it. An identity confirmation by mass spectrometry with the observed monoisotopic or average mass matching the expected value is the fifth item worth having, because it is the only one that distinguishes the intended molecule from a close analogue. Purity alone, however high, does not.
Worth restating the obvious: research-grade material of any salt form is not approved for human use, and none of the above turns a non-pharmaceutical powder into a medicine.
3The net-peptide arithmetic is the part I wish every COA reader saw first. 99% pure and 12% short at the same time. – sian_llewellyn 6 months ago 4Trifluoroacetate is the one to ask about explicitly. It is almost never volunteered. – elke_brunner 7 months ago add a comment