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Peptency Academy · Research progress

Impurity profiles of compounded and follow-on semaglutide: a 2026 LC-MS study

A 2026 Pharmaceutical Research study (PMID 42533250) detected 44 impurities in eight compounded semaglutide samples analysed by LC-MS; 34 were not identified in the originator product and 10 were at higher levels. Source sentenceResults: "44 impurities were detected in eight CPs assessed using LC-MS. Of these impurities, 34 were not identified in the originator semaglutide and 10 were present at higher levels in the CPs than the originator"1 Pharm Res 2026 Semaglutide is a GLP-1 receptor agonist peptide, also coded NN9535 (PubChem CID 56843331, formula C187H291N45O59, about 4114 Da). Source sentencePubChem CID 56843331: title Semaglutide; synonyms include NN9535; MolecularFormula C187H291N45O59; MolecularWeight 4114; PMID 42533250 abstract: "two glucagon-like peptide-1 receptor agonists (GLP-1 RAs): semaglutide and liraglutide"2 PubChem CID 568433311 Pharm Res 2026

Publication, Version 1Edited 5 sources

What happened

  • The authors report a component with a mass corresponding to tirzepatide in one compounded semaglutide sample and a component with a mass corresponding to insulin glulisine (PubChem CID 168324398) in another. Source sentenceResults: "an undisclosed component with a mass corresponding with tirzepatide detected" (CP9); "a component with mass corresponding to insulin glulisine were detected in CP10"1 Pharm Res 20263 PubChem CID 168324398
  • The study was published online on 30 Jul 2026 and compares follow-on and compounded semaglutide and liraglutide (PubChem CID 16134956) samples with the originator products (PMID 42533250, DOI 10.1007/s11095-026-04146-9). Source sentencePharm Res. 2026 Aug;43(8):2861-2886. Epub 2026 Jul 30. PURPOSE: "To assess impurity profiles/potential immunogenicity of multiple samples of follow-on or compounded products for two glucagon-like peptide-1 receptor agonists (GLP-1 RAs): semaglutide and liraglutide."1 Pharm Res 20264 PubChem CID 16134956
  • The samples came from 36 commercial suppliers in North and South America, Europe and Asia, including nine follow-on semaglutide drug substances and 13 compounded semaglutide products. Source sentenceMaterials for Remaining Assays: "obtained from 36 commercial suppliers across North and South America, Europe, and Asia (Table I). This included nine semaglutide DS follow-on products (S1 - S9), 13 ... semaglutide compounded products (CP: CP1 - CP13)"1 Pharm Res 2026
  • The methods were LC-MS impurity profiling, an MHC-II associated peptide proteomics assay (MAPPs) on dendritic cells from 15 healthy donors, photostability testing to ICH Q1B and a thioflavin T fibrillation assay. Source sentenceMETHODS: "Major histocompatibility complex-II-associated peptide proteomics assay (MAPPs), liquid chromatography-mass spectrometry analysis, photostability testing, and fibrillation assay were performed."; "Peripheral blood mononuclear cells were obtained from 15 healthy donors"; "Photostability testing was performed according to the International Council for Harmonization Q1B guideline"; "the thioflavin T (ThT) stress assay was performed to assess the physical stability of a representative selection of the liraglutide follow-on products"1 Pharm Res 2026
  • The paper states that the study was funded by Novo Nordisk A/S; nine of the ten authors are Novo Nordisk employees and shareholders, and the tenth is a shareholder who was an employee when the study was undertaken. Source sentencePMC13593678 full text, Funding: "This study was funded by Novo Nordisk A/S." Conflicts of Interest: "K.L.K., K.L., O.S., A.K.Ø., M.W., J.E.M., H.S.R.-A., C.L.S., and M.H. are employees and shareholders of Novo Nordisk A/S. A.S. is a shareholder of Novo Nordisk A/S and was an employee of Novo Nordisk A/S at the time that this study was undertaken."1 Pharm Res 2026

Why it matters for researchers

  • The published chromatograms separate identity from impurity profile: samples sold under one name held related forms of semaglutide, including dimers, trimers, oxidised forms and a formaldehyde adduct, and in two samples a second peptide. Source sentenceResults, Fig. 3: "the CP8 chromatogram showed covalent dimer and trimer forms that were not seen in the originator semaglutide"; "Exceedingly poor purity was seen in CP9, with oxidations, a semaglutide formaldehyde adduct, dimer, and trimer forms, and an undisclosed component with a mass corresponding with tirzepatide detected"1 Pharm Res 2026
  • It extends a 2024 Pharmaceutical Research analysis by an overlapping Novo Nordisk author group (PMID 39379664), which reported new impurities and impurity patterns in the follow-on semaglutide drug substances and products of one of the two product forms it analysed, and neoepitopes in follow-on samples. Source sentencePMID 39379664 abstract, Results: "Compared with originator, follow-on ... semaglutide DSs and DPs had new impurities and impurity patterns" (stated for one of the two semaglutide product forms analysed; the other form is described by quantity against label claim and dissolution); "Neoepitopes were identified in DS and DP semaglutide follow-ons"; authors include Hach M, Mogensen JE, Schelde O, Lamberth K, Staby A (Novo Nordisk A/S)5 Pharm Res 2024
  • Two samples from the same pharmacy, compounded one week apart, gave different impurity profiles, so a result describes one batch rather than a product name. Source sentenceResults: "Although CP2 and CP3 came from two different batches compounded 1 week apart from the same pharmacy, batch-to-batch variation in the impurity profiles was observed"1 Pharm Res 2026

What is not known

  • The authors state that a small number of samples were tested and that not every assay was run on every sample. Source sentenceDiscussion: "... a small number of samples were tested ... only some samples were tested using specific analytical tools"1 Pharm Res 2026
  • The study does not report immune responses in people; its immunogenicity data come from a cell based assay. Source sentenceMETHODS: MAPPs on monocyte-derived dendritic cells from healthy donors; CONCLUSIONS: "These results underscore the importance of in vitro immunogenicity assays/clinical immunogenicity studies"1 Pharm Res 2026
  • Products sold as research peptides were not part of the sample set; the samples were follow-on and compounded medicinal products. Source sentenceMaterials for Remaining Assays: "obtained from 36 commercial suppliers across North and South America, Europe, and Asia (Table I). This included nine semaglutide DS follow-on products (S1 - S9), 13 ... semaglutide compounded products (CP: CP1 - CP13)"1 Pharm Res 2026

Study record

  1. Analytical only (no biological model)Pharm Res 2026

    LC-MS impurity profiles, peptide presentation on donor dendritic cells (MAPPs), photostability and fibrillation of follow-on and compounded samples

    Design
    Comparative analytical study of marketed follow-on and compounded samples against the originator, plus an in vitro peptide presentation assay
    Population or model
    Follow-on drug substances and follow-on or compounded drug products from 36 suppliers; dendritic cells from 15 healthy donors for MAPPs
    Molecule
    semaglutide exact
    Comparator
    Originator semaglutide and liraglutide
    Funding
    Novo Nordisk A/S

    Funding statement: "This study was funded by Novo Nordisk A/S." Nine authors are employees and shareholders of Novo Nordisk A/S; one is a shareholder and was an employee when the study was undertaken.

    PubMed 42533250DOI

Sources

  1. 1Pharm Res 2026 accessed 13 Oct 2026
  2. 2PubChem CID 56843331 accessed 13 Oct 2026
  3. 3PubChem CID 168324398 accessed 13 Oct 2026
  4. 4PubChem CID 16134956 accessed 13 Oct 2026
  5. 5Pharm Res 2024 accessed 13 Oct 2026

About this page

Research-use information. This library summarises published literature and regulator records. It is not guidance for use, not medical advice, and not a statement that any material is suitable for use in people or animals.

Reviewed by the Peptency editorial process. Version 1, last edited 13 October 2026, 5 sources.

Cite this page: Peptency Academy. Semaglutide impurity profiles: compounded and follow-on samples. Version 1./eu/academy/news/semaglutide-impurity-profiles-compounded-follow-on/