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.

芳氧基丙醇胺是多种β-肾上腺素能受体拮抗剂（如美托洛尔）的必不可少的结构支架。具有这种结构基序的分子倾向于通过自由基引发的氧化途径降解为α，β-羟基丙醇胺杂质。这些杂质通常是极性和非发色的，因此，使用传统的反相色谱和UV检测常常会忽略不计。在这项工作中，美托洛尔的压力测试证实了3-异丙基氨基-1,2-丙二醇作为降解产物的产生，这是欧洲药典中指定的美托洛尔的杂质（杂质N）。为确保美托洛尔药品的安全性和质量，采用Halo Penta HILIC色谱柱（150 mm×4.6 mm，开发并优化了5μm）结合带电气溶胶检测（CAD）的方法，用于分离和定量美托洛尔药品（包括酒石酸美托洛尔，酒石酸美托洛尔和琥珀酸美托洛尔缓释片）中的美托洛尔杂质N. 这些HILIC-CAD方法已根据USP验证指南验证了特异性，线性，准确性和精密度，并已成功应用于确定美托洛尔药物产品中的杂质N。