Larazotide acetate — 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; aqueous-compatible phase
- Mobile phase and gradient
- A: 0.1 % trifluoroacetic acid in water; B: acetonitrile. Gradient 5–30 % B over 20 min
- Detection
- UV 214 nm only; no aromatic residue
- Retention
- Early
§6.2Identity by mass spectrometry
[M+H]⁺ at m/z 726.4. Average mass 725.8 ± 0.5 Da.[3]
§6.3Related substances and degradation
Table 7. Related substances recorded for Larazotide acetate, with the process or storage route that generates each and its analytical signature.
| Related substance | Origin | Analytical signature |
|---|---|---|
| Des-Gly1 or des-Gly2 truncation | Incomplete coupling | −57 Da; the N-terminal Gly-Gly motif is prone to incomplete coupling |
| Diketopiperazine at the Gln-Pro bond | Cyclisation | −18 Da; the Xaa-Pro motif again |
| Deamidated Gln6 | Storage | +1 Da |
| Acetate counter-ion | Supplied as the acetate salt | Acetate content must be quantified; the compound is defined as the acetate salt so the counter-ion is part of the specification rather than a residue |
Degradation routes
- Diketopiperazine formation
- Deamidation of Gln6
- Peptide-bond hydrolysis
- No oxidation-sensitive residues
§7Presentation, reconstitution and storage
§7.1Presentation and reconstitution
- Presentation
- Oral capsule (investigational)
- Reconstitution
- Not applicable — the compound acts in the intestinal lumen and injection would abolish its mechanism
- Storage, lyophilised
- −20 °C for research material
- Storage, reconstituted
- Not applicable
- In-use period
- Not applicable
This is the only compound in the series for which parenteral administration would be mechanistically self-defeating. The Institute records it because the point generalises: route is part of the pharmacology, not a matter of convenience.
§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.