Sermorelin — 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 (Tyr1, Tyr10)
- Retention
- Intermediate
§6.2Identity by mass spectrometry
[M+3H]³⁺ at m/z ≈ 1120.0; deconvoluted average mass 3357.9 ± 2 Da.[3]
§6.3Related substances and degradation
Table 7. Related substances recorded for Sermorelin, with the process or storage route that generates each and its analytical signature.
| Related substance | Origin | Analytical signature |
|---|---|---|
| GRF(3-29) truncation | DPP-4 cleavage during handling, or incomplete synthesis | −234 Da; biologically inactive and the single most important impurity to quantify |
| C-terminal free acid | Incomplete amidation | +0.98 Da; substantially reduces potency |
| Met27 sulfoxide | Oxidation | +16 Da |
| Deamidated Asn8, Gln16, Gln24 | Storage | +1 Da each |
| Acetate counter-ion | Purification | Sermorelin is conventionally supplied as the acetate; acetate content of 5–10 % by mass is expected and must be quantified, not ignored |
Degradation routes
- N-terminal cleavage is the dominant route and occurs in solution even without enzymatic activity at elevated temperature
- Methionine oxidation
- Deamidation
- Loss of the C-terminal amide
§7Presentation, reconstitution and storage
§7.1Presentation and reconstitution
- Presentation
- Lyophilised powder for reconstitution
- Reconstitution
- A 5 mg vial with 2.5 mL gives 2 mg/mL; a 200 µg dose is then 0.10 mL, that is 10 units on a U-100 syringe.
- Storage, lyophilised
- 2–8 °C for the historical approved product; −20 °C for research material
- Storage, reconstituted
- 2–8 °C, and the Institute notes that no published stability-indicating data support extended refrigerated storage of reconstituted sermorelin
- In-use period
- No supported in-use claim
Sermorelin is the clearest illustration in this series of the gap between an established diagnostic evidence base and a marketed therapeutic claim. The Institute assesses the two separately and rates them very differently.
§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.