Semaglutide

1 Identity

Acylated lipopeptide, not a plain peptide, and describing it by residue count alone is the error that lets a des-acyl lot pass release. A 31-residue GLP-1(7-37) backbone carrying two substitutions — Ala8 replaced by the non-proteinogenic 2-aminoisobutyric acid and Lys34 replaced by Arg — with a lipid side chain on the epsilon-amine of Lys26, the only lysine remaining in the molecule because position 34 was substituted away. Free-acid C-terminal glycine, free N-terminal alpha-amine, no cysteine, no disulfide and no sulfur atom anywhere. and as the active moiety of three approved US drug products marketed as Ozempic. CAS 910463-68-2 for the free acid. PubChem CID 56843331. One reagent catalog splits the same entity across four catalog numbers by counter-ion — free acid, acetate, sodium salt and trifluoroacetate.

Sequence

H-His-Aib-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Arg-Gly-Arg-Gly-OH; one-letter H-{Aib}EGTFTSDVSSYLEGQAAKEFIAWLVRGRG-OH, 31 residues. Side chain: Lys26-N(epsilon)-(AEEA-AEEA-gamma-Glu-C18 di-acid), that is the epsilon-amine acylated through two 8-amino-3,6-dioxaoctanoic acid units and a gamma-glutamate spacer to octadecanedioic acid. The acylation site is part of the identity of the molecule and is not established by intact mass.

Molecular formula

C187H291N45O59 (free acid). The composition decomposes as a backbone of C152H230N42O47 plus a side-chain increment of C35H61N3O12, and the increment itself as C18H32O3 plus C5H7NO3 plus two units of C6H11NO3, so the arithmetic can be checked rather than trusted. The absence of sulfur is an analytical asset and is used in the variant arithmetic.

Average mass

4113.641 Da (C187H291N45O59) on IUPAC 2021 abridged conventional atomic weights. One seller publishes 4113.6 and PubChem 4114; the same formula on the pre-2021 table returns 4113.578, so the published figures bracket the same composition rather than disagreeing about it. Salt forms have no single average mass and are recorded as formula plus a measured stoichiometry, which is exactly how the supplier writes them: acetate as C187H291N45O59 - XC2H4O2 and trifluoroacetate as C187H291N45O59 - XCF3COOH, with X left unassigned because it is measured and not constant. One hydrogen decides this figure: subtracting a hydrogen for the amide bond that the side-chain increment already accounts for gives C187H290N45O59 at 4112.633, and a one-hydrogen slip is the exact class of error that survives onto a certificate.

Monoisotopic mass

4111.11538 Da neutral free acid; [M+H]+ 4112.12265; [M+4H]4+ 1028.78612; [M+5H]5+ 823.23035 (monoisotopic). At this mass a plus or minus 5 ppm window on the protonated ion is plus or minus 0.021 Da, which cannot exclude a single deamidation and certainly cannot resolve a positional isomer; intact mass is deconvoluted from the charge-state envelope and read alongside the peptide map, never instead of it.

Salt / variant note

Six distinct commercial articles carry this name, four of them from one reagent catalog alone, and the differences are measurable. Salt forms first, because the product name rarely states them: free acid, C187H291N45O59, 4113.6; acetate, written by the supplier as C187H291N45O59 - XC2H4O2 with the molecular weight still quoted as 4113.6; sodium salt; trifluoroacetate, written C187H291N45O59 - XCF3COOH, molecular weight again 4113.6. Four catalog articles, four prices, one molecular entity, and three of the four have no single true molecular weight — the supplier's own X is the honest notation and it is the notation this catalog adopts. Counter-ion arithmetic on the free acid: 1 mol acetate is 1.44 percent w/w of the salt, 2 mol 2.84 percent, 3 mol 4.20 percent; 1 mol trifluoroacetate 2.70 percent, 2 mol 5.25 percent, 3 mol 7.68 percent. Molecular substitutions: des-acyl semaglutide, C152H230N42O47, 3397.759 avg / 3395.68985 mono — the side chain is 715.88 Da, 17.4 percent of the whole molecule, and a des-acyl lot still elutes as one sharp peak and passes area-percent purity at 99 percent; this is the failure mode the panel exists for. The His7 alpha-amine positional isomer, acylated on the N-terminal alpha-amine instead of the Lys26 epsilon-amine, has an identical formula and an identical mass to the last decimal, and only Lys-C or tryptic mapping with MS/MS separates them; the Lys34-to-Arg substitution is what makes this the live risk, because it leaves exactly one lysine competing with the N-terminus. Di-acylated species, C222H352N48O71, 4829.523 avg / 4826.54090 mono, +715.88. Liraglutide, C172H265N43O51, 3751.262 avg / 3748.94646 mono — 362.38 Da lighter, a shorter acyl group at the same backbone position, and the cheapest available substitute. Des-(7-13) semaglutide is sold as a catalog impurity standard at a supplier-stated C156H246N38O45, 3373.9, at least 90 percent, and that formula does not reconcile with the parent by residue subtraction: deleting His7-Aib8-Glu9-Gly10-Thr11-Phe12-Thr13 (residue sum C34H47N9O11, 757.80) from C187H291N45O59 gives C153H244N36O48 at 3355.84, which differs from the published composition by C3H2N2O-3. Nothing is asserted beyond the supplier's own figures — the article is real and purchasable and its published formula is internally consistent with its published mass at 3373.905 — but the deletion the name implies is not the deletion the formula describes, so the data sheet must be obtained before that standard is used to qualify anything.

2 Class & testing panel

Form

Single article

Testing panel

P2 — panel definition

3 Primary sources & evidence

The index reports the design and provenance of the literature, not a conclusion about effect.

This is the entry where the human evidence base is large, and it belongs to the approved finished products rather than to bulk material of unverified provenance. The sponsor program comprises multiple randomized, double-blind, placebo- and active-controlled phase 3 trials enrolling tens of thousands of participants in aggregate, anchored by the SUSTAIN, PIONEER, step and SELECT publication series in the New England Journal of Medicine and The Lancet from 2016 onward. What does not exist is any study of gray-market semaglutide API: no published characterization of bulk material sold outside the approved supply chain, no chain-of-custody data and no impurity profiling of it. The citation index page states both halves and states the inference rule between them — trial evidence generated on an approved finished product is not evidence about a different article of unknown composition and unknown acylation site.

4 Storage & specification

Storage

Acylated GLP-1 peptides are surface-active and adsorb to glass, so the article is filled into low-adsorption or siliconized vials and stored at -20 degrees C plus or minus 5 degrees C, desiccated and protected from light. The recovery check is performed on the actual container-closure system in use rather than assumed from another product.

Shelf life

The retest date on a lot is a conclusion from stability testing on the filled container-closure system above, not a transcription of a supplier's handling note. The attributes that limit the interval are the ones this molecule fails on: des-acyl content, di-acylated species, deamidation, and any shift in the acylation-site profile, read from the reversed-phase purity method and the Lys-C or tryptic peptide map together, since intact mass alone resolves none of them. Lots rotate first-expiry-first-out on that date.