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Quantitative analysis of 3-isopropylamino-1,2-propanediol as a degradation product of metoprolol in pharmaceutical dosage forms by HILIC-CAD / 药物分析学报
Article en Zh | WPRIM | ID: wpr-823976
Biblioteca responsable: WPRO
ABSTRACT
Aryloxypropanolamine is an essential structural scaffold for a variety of β-adrenergic receptor antago-nists such as metoprolol. Molecules with such a structural motif tend to degrade into α, β-hydroxypropanolamine impurities via a radical-initiated oxidation pathway. These impurities are typically polar and nonchromophoric, and are thus often overlooked using traditional reversed phase chromatography and UV detection. In this work, stress testing of metoprolol confirmed the generation of 3-isopropylamino-1,2-propanediol as a degradation product, which is a specified impurity of metoprolol in the European Pharmacopoeia (impurity N). To ensure the safety and quality of metoprolol drug products, hydrophilic interaction chromatography (HILIC) methods using Halo Penta HILIC column (150 mm×4.6 mm, 5 μm) coupled with charged aerosol detection (CAD) were developed and optimized for the separation and quantitation of metoprolol impurity N in metoprolol drug products including metoprolol tartrate injection, metoprolol tartrate tablets, and metoprolol succinate extended-release tablets. These HILIC-CAD methods were validated per USP validation guidelines with respect to speci-ficity, linearity, accuracy, and precision, and have been successfully applied to determine impurity N in metoprolol drug products.
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Texto completo: 1 Base de datos: WPRIM Idioma: Zh Revista: Journal of Pharmaceutical Analysis Año: 2019 Tipo del documento: Article
Texto completo: 1 Base de datos: WPRIM Idioma: Zh Revista: Journal of Pharmaceutical Analysis Año: 2019 Tipo del documento: Article