Methoxypropylamino Cyclohexenylidene Ethoxyethylcyanoacetate
Compositional guideline for Methoxypropylamino Cyclohexenylidene Ethoxyethylcyanoacetate permitted for use in listed medicines
Description
Methoxypropylamino Cyclohexenylidene Ethoxyethylcyanoacetate is produced by chemical synthesis. Subsequent washing and solvent elimination yield the desired substance in not less than 97% purity. The obtained substance is an isomeric mixture with a ratio of 1.98 : 1.00 for Z-isomer to E-isomer.
- Chemical Name: 2-Ethoxyethyl (2Z)-2-cyano-2-[3-(3-methoxypropylamino)cyclohex-2-en-1-ylidene]acetate
- Molecular formula: C17H26N2O4
- CAS number: 1419401-88-9
- Molecular weight: 322.41 g/mol
| Test | Method reference | Acceptance criteria |
|---|---|---|
| Characterisation | ||
| General properties | ||
| Appearance | Visual | Yellowish to yellow powder |
| Melting point | BP (Appendix V A) | 85 -120°C |
| Particle size | USP <786> | D(0.5) ≥1.2 µm |
| Solubility in Water | Commission Directive 92/69/EEC (1992) - Flask Method A6 | 0.45 g/L at 20°C |
| pH (1% in water) | Ph. Eur. 2.2.3 | 5.8-5.9 |
| Water content | Karl Fischer (Ph. Eur. 2.5.12) | ≤0.13% (w/w) |
| Identity | ||
| FT-IR | USP <854>; Ph. Eur. 2.2.40 | Observation of characteristic peaks at 2187, 1675, 1493, 1458, 1428, 1386, 1323, 1284, 1199, 1187, 1109, 1065, and 1025 cm-1. |
| HPLC-MS | HPLC-MS (Ph. Eur. 2.2.46; Ph. Eur. 2.2.29; Ph. Eur. 2.2.43) | The retention time of the main component corresponds to the retention time of the standard ±3%. Detection of molecular ions peaks as follows:
|
| UV/Vis (in ethanol) | USP <857> | The spectrum should cover whole UV-A region (320-400 nm) and most of the UV-B region (290-320 nm) with λmax at 385 nm ± 5 nm. Observation of two other peaks at 228.4 nm and 459.5 nm |
| Assay | ||
| Assay | HPLC-UV/Vis (Ph. Eur. 2.2.46; Ph. Eur. 2.2.29) | ≥97.0% |
| Impurities and incidental constituents | ||
| Residual Solvents | ||
| Class 2 solvents | Headspace-GC-MS (Ph. Eur. 2.2.28; Ph. Eur. 2.4.24) | ≤50 ppm |
| Elemental impurities | ||
| Arsenic | ICP-OES (ISO 11885/ISO 17294/ISO 21392) | ≤1 ppm |
| Lead | ICP-OES (ISO 11885/ISO 17294/ISO 21392) | ≤5 ppm |
| Nickel | ICP-OES (ISO 11885/ISO 17294/ISO 21392) | ≤2 ppm |
| Cadmium | ICP-OES (ISO 11885/ISO 17294/ISO 21392) | ≤2 ppm |
| Antimony | ICP-OES (ISO 11885/ISO 17294/ISO 21392) | ≤2 ppm |
| Mercury | ICP-OES (ISO 11885/ISO 17294/ISO 21392) | ≤1 ppm |
| Chromium | ICP-OES (ISO 11885/ISO 17294/ISO 21392) | ≤5 ppm |
| Cobalt | ICP-OES (ISO 11885/ISO 17294/ISO 21392) | ≤2 ppm |
| Other organic or inorganic impurities or toxins | ||
| Sum of impurities >0.1% | HPLC-UV/Vis (Ph. Eur. 2.2.46; Ph. Eur. 2.2.29) | ≤0.5% |
| Sum of impurities <0.1% | HPLC-UV/Vis (Ph. Eur. 2.2.46; Ph. Eur. 2.2.29) | ≤0.2% |
| 2-Ethoxyethanol | GC-FID (Ph. Eur. 2.2.28) | < 20 ppm |
| 3-methoxypropylamine | GC-FID (Ph. Eur. 2.2.28) | ≤500 ppm |
| Diethyl sulfate | Headspace-GC-MS (Ph. Eur. 2.2.28; Ph. Eur. 2.4.24) | <1 ppm |
| Nitrosamines | Challis et al., 1995[1] | <50 ppb |
Footnotes
Challis, B. C., Colling, J., Cromie, D. D. O., Guthrie, W. G., Pollock, J. R. A., Taylor, P., Telling, G. M., Wallace, L. (1995) A screening procedure for total N‐nitroso contaminants in personal care products: results of collaborative studies undertaken by a CTPA Working Group. International journal of cosmetic science, 17(6), 219-231.
Abbreviations
- BP: British Pharmacopoeia
- FID: Flame Ionisation Detection
- GC: Gas Chromatography
- HPLC: High Performance Liquid Chromatography
- ICP: Inductively Coupled Plasma
- ISO: International Organisation for Standardisation
- MS: Mass Spectrometry
- OES: Optical Emission Spectrometry
- Ph. Eur.: European Pharmacopoeia
- UPLC: Ultra Performance Liquid Chromatography
- USP: United States Pharmacopeia
- UV/Vis: Ultraviolet-Visible Spectroscopy/Detection.