5-amino-1MQ — analytical characterisation
Chromatographic conditions, identity, related substances, presentation, reconstitution and in-use stability.
§6Analytical characterisation
§6.1Chromatographic conditions
- Column
- C18 or a mixed-mode phase; a permanently charged quaternary cation requires either ion pairing or a phase tolerant of cationic analytes
- Mobile phase and gradient
- A: 20 mM ammonium formate pH 3.5; B: acetonitrile. Gradient 5–40 % B over 12 min
- Detection
- UV 254 nm and 340 nm; the aminoquinolinium chromophore is strong and highly diagnostic, and the full diode-array spectrum is a robust identity check
- Retention
- Early to intermediate depending on ion-pairing conditions
§6.2Identity by mass spectrometry
The cation is observed directly at m/z 159.1 in positive mode without protonation, since it carries a permanent charge — a distinctive behaviour that itself confirms the quaternary structure.[3]
§6.3Related substances and degradation
Table 7. Related substances recorded for 5-amino-1MQ, with the process or storage route that generates each and its analytical signature.
| Related substance | Origin | Analytical signature |
|---|---|---|
| Regioisomers (amino group at a different ring position) | Synthesis | Isobaric; require chromatographic resolution. The 5-amino regiochemistry is the basis of the reported activity and other isomers are not equivalent |
| Non-methylated 5-aminoquinoline | Incomplete quaternisation | −14 Da and a neutral rather than permanently charged species with entirely different properties |
| Residual iodide or alternative counter-ion | Salt form | Iodide content should be quantified; the salt form must be stated because it determines the mass correction from salt to cation |
| Residual solvents | Process | Headspace gas chromatography |
| Elemental impurities | Synthesis | Not generally reported |
Degradation routes
- Photodegradation of the quinolinium chromophore under light
- Oxidation of the aromatic amine to coloured products, visible as darkening of the solid
- No peptide degradation routes apply
§7Presentation, reconstitution and storage
§7.1Presentation and reconstitution
- Presentation
- Crystalline powder, typically the iodide salt; oral capsules
- Reconstitution
- Not conventionally reconstituted for injection. Where a mass is stated, the salt-to-cation correction is substantial: 286.11 g/mol for the iodide against 159.21 for the cation means only 55.6 % of the salt mass is the active cation. A certificate that does not state the salt form has left a 44 % ambiguity in the dose.
- Storage, lyophilised
- Room temperature or 2–8 °C, desiccated and protected from light
- Storage, reconstituted
- Not applicable
- In-use period
- Not applicable
The salt-form arithmetic here is the clearest case in the series of why the counter-ion is part of the specification. A gram of 5-amino-1MQ iodide and a gram of the cation are not the same quantity of compound, and the difference is not a rounding error.
§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.