Orforglipron — analytical characterisation
Chromatographic conditions, identity, related substances, presentation, reconstitution and in-use stability.
§6Analytical characterisation
§6.1Chromatographic conditions
- Column
- C18, 2.1 × 100 mm, 1.8 µm — a conventional small-molecule reverse-phase method
- Mobile phase and gradient
- A: 10 mM ammonium formate pH 3.5; B: acetonitrile. Gradient 30–95 % B over 12 min
- Detection
- UV 254 nm and 280 nm; diode-array purity check across 210–400 nm
- Retention
- Single sharp peak; peak shape and symmetry are more informative than for peptides
§6.2Identity by mass spectrometry
ESI positive mode [M+H]⁺ at m/z 752.3. A small molecule gives a single dominant ion rather than a charge envelope; a certificate showing a peptide-style charge envelope for orforglipron indicates the wrong substance entirely.[3]
§6.3Related substances and degradation
Table 7. Related substances recorded for Orforglipron, with the process or storage route that generates each and its analytical signature.
| Related substance | Origin | Analytical signature |
|---|---|---|
| Regioisomeric and diastereomeric by-products | Synthesis | Isobaric — require chromatographic resolution, not mass |
| Residual palladium or other catalyst | Coupling chemistry | Inductively coupled plasma mass spectrometry; not a peptide concern and frequently omitted from research-supply certificates |
| Residual solvents | Process | Headspace gas chromatography per ICH Q3C |
Degradation routes
- Photodegradation of the fluorinated aromatic system under light stress
- Hydrolysis of the amide linkages under strongly acidic or basic conditions
- No aggregation or deamidation routes — the peptide degradation framework does not apply
§7Presentation, reconstitution and storage
§7.1Presentation and reconstitution
- Presentation
- Oral tablet (investigational)
- Reconstitution
- Not applicable
- Storage, lyophilised
- Room temperature in a closed container, protected from light
- Storage, reconstituted
- Not applicable
- In-use period
- Not applicable
Because this is a small molecule, the Institute applies the small-molecule minimum data standard: identity by two orthogonal methods, assay against a reference standard, related substances, residual solvents, and elemental impurities. The peptide minimum data standard does not apply and a peptide-style certificate is recorded as not conformant.
§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.