Cagrilintide — analytical characterisation
Chromatographic conditions, identity, related substances, presentation, reconstitution and in-use stability.
§6Analytical characterisation
§6.1Chromatographic conditions
- Column
- C18, 2.1 × 150 mm, 1.7 µm
- Mobile phase and gradient
- A: 0.1 % trifluoroacetic acid in water; B: acetonitrile with 0.1 % trifluoroacetic acid. Gradient 20–55 % B over 30 min
- Detection
- UV 214 nm; 280 nm weak (limited aromatic content)
- Retention
- Intermediate; the low aromatic content makes 280 nm detection insensitive and UV 214 nm mandatory
§6.2Identity by mass spectrometry
Charge envelope dominated by [M+3H]³⁺. The Institute notes that published mass values for this compound are inconsistent across secondary sources and that supplier certificates should be compared against a primary reference standard rather than against a catalogue figure.[3]
§6.3Related substances and degradation
Table 7. Related substances recorded for Cagrilintide, with the process or storage route that generates each and its analytical signature.
| Related substance | Origin | Analytical signature |
|---|---|---|
| Amyloidogenic sequence reversion | Incorrect substitution in the 20–29 region | May not be resolvable by mass alone if the substitution is isobaric; orthogonal sequencing is required |
| Non-acylated backbone | Failed conjugation | Large negative mass shift |
| Aggregated high-molecular-weight species | Process or storage | Detected by size-exclusion chromatography, not by reverse phase |
Degradation routes
- Aggregation is the principal stability concern for any amylin analogue and is not detected by reverse-phase purity assay alone
- Deamidation of Asn residues on aqueous storage
§7Presentation, reconstitution and storage
§7.1Presentation and reconstitution
- Presentation
- Investigational solution for injection; lyophilised powder in research supply
- Reconstitution
- A 5 mg vial reconstituted with 1.0 mL gives 5 mg/mL; 0.5 mg is then 0.10 mL, that is 10 units on a U-100 syringe.
- Storage, lyophilised
- 2–8 °C; −20 °C for extended storage
- Storage, reconstituted
- 2–8 °C
- In-use period
- No published in-use data
Because the class is inherently aggregation-prone, the Institute regards a size-exclusion chromatography result as a necessary complement to reverse-phase purity for any amylin analogue. Certificates reporting only reverse-phase purity are recorded as incomplete for this class.
§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.