What semaglutide is
Semaglutide is a synthetic analogue of human glucagon-like peptide-1 (GLP-1), 31 amino acids long, developed at Novo Nordisk as a long-acting agonist of the GLP-1 receptor. It is the most thoroughly characterised compound in the incretin-analogue class and the comparator against which the dual and triple agonists, including tirzepatide and retatrutide, are usually measured.
Three changes distinguish it from the native hormone. Alanine at position 8 is replaced by 2-aminoisobutyric acid, which blocks cleavage by DPP-4. Lysine at position 34 is replaced by arginine so that the chain has only one lysine. That remaining lysine, at position 26, carries a C18 fatty diacid attached through a γ-glutamate and two short polyethylene-glycol spacers; the diacid binds reversibly to serum albumin and is responsible for its half-life of roughly a week. The average molecular weight is approximately 4,114 g/mol and the CAS number is 910463-68-2.
The published literature on the compound, with references, is collected in the monograph.
What you receive
Each vial contains semaglutide as a white to off-white lyophilised powder, sealed with a flip-off cap over a crimped stopper, in the net quantity stated on the label: 10, 15 or 20 mg. There is no carrier, mannitol or other excipient unless the batch certificate says otherwise. The batch number is printed on the label and matches the certificate in our register.
Reading the certificate for a semaglutide batch
Purity by reversed-phase HPLC is reported as the area of the main peak against all peaks and should be above 99% for a well-made lot. Identity by LC-MS is reported as the observed mass against the expected mass of about 4,114 Da. The lipid, γ-glutamate and spacers together contribute several hundred daltons, so a batch in which the modification is missing or incomplete fails this check unambiguously; the mass is also sensitive to the Aib and arginine substitutions. Net peptide content gives the milligrams of peptide actually in the vial, which differs from the gross weight because lyophilised peptides retain water and counter-ions.
The impurities most often seen with semaglutide are deletion sequences, a small amount of des-lipidated peptide, and oxidation at the tryptophan residue, all of which elute close to the main peak. At the sub-1% level these are normal. Our guide to reading a certificate of analysis shows annotated examples, and HPLC and LC-MS explained describes the methods.
Storage and handling
Sealed vials should be kept refrigerated at 2 to 8 °C and protected from light; −20 °C is preferable for storage beyond a few months. The lyophilised powder is stable for well over a year under those conditions. The lipidated chain is somewhat hygroscopic, so allow the vial to reach room temperature before opening to avoid condensation. Semaglutide is soluble at neutral and mildly alkaline pH but less so near its isoelectric point, which is worth bearing in mind when choosing a buffer. Reconstituted solutions should be prepared fresh or aliquoted and frozen; the storage and stability guide covers solvents and freeze-thaw behaviour.
