LC-UV/MS quality analytics of paediatric artemether formulations
- Author:
Vandercruyssen Kirsten
;
D’Hondt Matthias
;
Vergote Valentijn
;
Jansen Herwig
;
Burvenich Christian
;
Spiegeleer De Bart
- Publication Type:Journal Article
- Keywords:
Paediatric formulations;
Sample preparation;
Polar embedded organic acid column;
Artemisinin trioxane derivatives;
Related impurities and degradation compounds;
MS-fragmentation
- From:
Journal of Pharmaceutical Analysis
2014;(1):37-52
- CountryChina
- Language:Chinese
-
Abstract:
A highly selective and stability-indicating HPLC-method, combined with appropriate sample preparation steps, is developed for β-artemether assay and profiling of related impurities, including possible degradants, in a complex powder for oral suspension. Following HPLC conditions allowed the required selectivity: a Prevail organic acid (OA) column (250 mm×4.6 mm, 5μm), flow rate set at 1.5 mL/min combined with a linear gradient (where A ? 25 mM phosphate buffer (pH 2.5), and B ? acetonitrile) from 30% to 75% B in a runtime of 60 min. Quantitative UV-detection was performed at 210 nm. Acetonitrile was applied as extraction solvent for sample preparation. Using acetonitrile-water mixtures as extraction solvent, a compartmental behaviour by a non-solving excipient-bound fraction and an artemether-solubilising free fraction of solvent was demonstrated, making a mobile phase based extraction not a good choice. Method validation showed that the developed HPLC-method is considered to be suitable for its intended regulatory stability-quality characterisation of β-artemether paediatric formulations. Furthermore, LC-MS on references as well as on stability samples was performed allowing identity confirmation of the β-artemether related impurities. MS-fragmentation scheme of β-artemether and its related substances is proposed, explaining the m/z values of the in-source fragments obtained.
