Quantitative analysis of 3-isopropylamino-1,2-propanediol as a degradation product of metoprolol in pharmaceutical dosage forms by HILIC-CAD  

作　　者：Qun Xu Shane Tan 

机构地区：[1]Compendial Development Laboratory,United States Pharmacopeial Convention (USP)

出　　处：《Journal of Pharmaceutical Analysis》2019年第6期431-436,共6页药物分析学报（英文版）

摘　　要：Aryloxypropanolamine is an essential structural scaffold for a variety of b-adrenergic receptor antagonists such as metoprolol.Molecules with such a structural motif tend to degrade into α,β ehydroxypropanolamine impurities via a radicaleinitiated 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(150mm×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 specificity,linearity,accuracy,and precision,and have been successfully applied to determine impurity N in metoprolol drug products.Aryloxypropanolamine is an essential structural scaffold for a variety of β-adrenergic receptor antagonists 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 specificity,linearity,accuracy,and precision,and have been successfully applied to determine impurity N in metoprolol drug products.

关 键 词：Hydrophilic interaction chromatography(HILIC) Charged aerosol detection(CAD) Metoprolol tartrate injection Metoprolol tartrate tablets Metoprolol succinate extended-release tablets 

分 类 号：O65[理学—分析化学]