Teduglutide — analytical characterisation
Chromatographic conditions, identity, related substances, presentation, reconstitution and in-use stability.
§6Analytical characterisation
§6.1Chromatographic conditions
- Column
- C18, 4.6 × 250 mm, 5 µm
- Mobile phase and gradient
- A: 0.1 % trifluoroacetic acid in water; B: acetonitrile. Gradient 20–45 % B over 30 min
- Detection
- UV 214 nm; 280 nm (Trp31, Phe residues)
- Retention
- Intermediate; no lipid conjugate
§6.2Identity by mass spectrometry
[M+3H]³⁺ at m/z ≈ 1251.7; deconvoluted average mass 3752.1 ± 2 Da. Note the near-coincidence with liraglutide’s average mass of 3751.2 — a difference of under 1 Da that a low-resolution instrument will not distinguish. The Institute regards this as a concrete example of why nominal mass agreement is not identity confirmation.[3]
§6.3Related substances and degradation
Table 7. Related substances recorded for Teduglutide, with the process or storage route that generates each and its analytical signature.
| Related substance | Origin | Analytical signature |
|---|---|---|
| Met10 sulfoxide | Oxidation | +16 Da; the principal storage impurity |
| Deamidated Asn/Gln forms | Storage | +1 Da |
| Des-His1 truncation | Degradation or incomplete coupling | −137 Da |
| Liraglutide cross-contamination or substitution | Shared facility, or deliberate substitution | Average masses differ by less than 1 Da; requires high-resolution MS or peptide mapping to exclude |
Degradation routes
- Methionine oxidation
- Deamidation
- Aggregation at elevated concentration
§7Presentation, reconstitution and storage
§7.1Presentation and reconstitution
- Presentation
- Lyophilised powder for reconstitution in a single-dose vial (approved product)
- Reconstitution
- The approved product is supplied as a lyophilate reconstituted with the provided diluent to 10 mg/mL; a 0.05 mg/kg dose for a 70 kg adult is 3.5 mg, that is 0.35 mL or 35 units on a U-100 syringe.
- Storage, lyophilised
- Below 25 °C
- Storage, reconstituted
- Use within three hours of reconstitution; do not freeze
- In-use period
- Three hours after reconstitution for the approved product
The three-hour in-use limit for the approved product is a useful benchmark: it indicates that the manufacturer, with full stability data, does not claim extended in-use stability for a reconstituted peptide at room temperature.
§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.