Validated, stability-indicated quantitative purity test for triethylenetetramine tetrachlorhydrate by automated
C Dauphin1, D Poirier, D Pradeau
1AGEPS, 7 Rue du Fer à Moulin, 75221 Paris Cedex 05, France. Chantal.dauphin@eps.aphp.fr
Journal of Chromatographic Science
|July 14, 2007
Summary
A new quantitative purity test for triethylene tetramine tetrachlorhydrate (Trientine) was developed using automated multiple development high-performance thin-layer chromatography. This method offers reliable and accurate impurity detection for Wilson's disease treatment.
Area of Science:
- Pharmaceutical analysis
- Analytical chemistry
- Pharmacology
Background:
- Triethylenetetramine dihydrochloride (Trientine) is in the US Pharmacopeia, but not the European Pharmacopeia.
- Triethylene tetramine tetrachlorhydrate, used by AGEPS, is more soluble than the dihydrochloride form.
- Trientine is a treatment for Wilson's disease, a genetic disorder of copper metabolism.
Purpose of the Study:
- To develop and validate a quantitative purity test for triethylene tetramine tetrachlorhydrate.
- To establish a reliable method for detecting impurities in trientine formulations.
- To address the lack of a European Pharmacopeia monograph for trientine salts.
Main Methods:
- Development and validation of a quantitative purity test using automated multiple development high-performance thin-layer chromatography (AMD-HPTLC).
- Validation parameters included retention factor, linearity, limits of detection and quantitation, reliability, and accuracy.
- Comparison with existing methods, including the US Pharmacopeia monograph for triethylenetetramine dihydrochloride and high-performance liquid chromatography (HPLC).
Main Results:
- A validated quantitative purity test for triethylene tetramine tetrachlorhydrate was successfully developed using AMD-HPTLC.
- The method demonstrated reliability and accuracy, with limits of detection and quantitation in the nanogram range.
- Existing methods, including the US Pharmacopeia monograph and HPLC, were insufficient for quantitative impurity separation and validation.
Conclusions:
- Automated multiple development high-performance thin-layer chromatography provides a validated, quantitative method for assessing the purity of triethylene tetramine tetrachlorhydrate.
- This method is crucial for ensuring the quality of trientine used in treating Wilson's disease.
- Further development is needed for comparative validation of impurity separation using other chromatographic techniques.
