Semaglutide, oral — analytical characterisation
Chromatographic conditions, identity, related substances, presentation, reconstitution and in-use stability.
§6Analytical characterisation
§6.1Chromatographic conditions
- Column
- C18, 4.6 × 150 mm, 3.5 µm
- Mobile phase and gradient
- As for subcutaneous semaglutide, with an additional isocratic method for SNAC quantification at 240 nm
- Detection
- UV 214 nm for peptide; 240 nm for SNAC
- Retention
- Peptide as for the subcutaneous product; SNAC elutes early and must be resolved from the void
§6.2Identity by mass spectrometry
Identical peptide mass envelope. SNAC gives [M−H]⁻ at m/z 292.1 in negative mode.[3]
§6.3Related substances and degradation
Table 7. Related substances recorded for Semaglutide, oral, with the process or storage route that generates each and its analytical signature.
| Related substance | Origin | Analytical signature |
|---|---|---|
| Free salicylamide from SNAC hydrolysis | Excipient degradation | Detectable at 240 nm; not a peptide impurity |
| All semaglutide peptide impurities | See semaglutide monograph | Identical profile |
Degradation routes
- Tablet-level dissolution failure is the dominant quality risk rather than peptide degradation
- Moisture uptake causes SNAC hydrolysis and loss of permeation-enhancing capacity
§7Presentation, reconstitution and storage
§7.1Presentation and reconstitution
- Presentation
- Immediate-release tablet, 3 mg, 7 mg, 14 mg (diabetes) and 25 mg, 50 mg (obesity programme)
- Reconstitution
- Not applicable — solid oral dosage form
- Storage, lyophilised
- Below 30 °C in the original blister; protect from moisture
- Storage, reconstituted
- Not applicable
- In-use period
- Not applicable
Dividing, crushing or chewing the tablet is not permitted; the absorption mechanism depends on the intact tablet creating a local high-concentration microenvironment.
§7.2In-use stability
Applicable standards: CEI-MS-01 · CEI-MS-02 · CEI-MS-03 · CEI-MS-04 · CEI-MS-05 · CEI-MS-06. The full series is at methodological standards.
Working calculators: reconstitution and insulin-unit conversion · purity against peptide content · certificate minimum-data checker.
References cited on this page
References are numbered in order of first citation in this document. Each superscript in the text links to its entry below.
- United States Pharmacopeial Convention. General Chapter ⟨1225⟩ Validation of Compendial Procedures. United States Pharmacopeia — National Formulary (USP–NF) 2024;USP 2024 Issue 1. identifier not held by the Institute
- International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. ICH Q2(R2) Validation of Analytical Procedures. ICH Harmonised Guideline 2023;Step 4 version, 1 November 2023. identifier not held by the Institute
- International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. ICH Q6B Specifications: Test Procedures and Acceptance Criteria for Biotechnological/Biological Products. ICH Harmonised Tripartite Guideline 1999;Step 4 version. identifier not held by the Institute
- International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. ICH Q1A(R2) Stability Testing of New Drug Substances and Products. ICH Harmonised Tripartite Guideline 2003;Step 4 version. identifier not held by the Institute
- Manning MC, Chou DK, Murphy BM, Payne RW, Katayama DS. Stability of protein pharmaceuticals: an update. Pharmaceutical Research 2010;27(4):544–575. doi:10.1007/s11095-009-0045-6 · PMID 20143256
Identifiers are reproduced only where the Institute holds them. Where a digital object identifier or PubMed identifier is not shown, the Institute has recorded the journal and year and has not constructed an identifier.