Abstract

The objective of the present work was to develop a sensitive, selective, accurate and precise stability-indicating HPLC method for quantification of degradation products and process-related impurities in fesoterodine fumarate extended-release tablets. The degradation profile was studied by conducting forced degradation studies and all the degradation products formed during degradation were separated. A chromatographic separation was achieved by using Waters Symmetry C18, 250 × 4.6 mm, 5 μm column, maintained at 30°C. Mobile phase A (0.05% trifluoroacetic acid in water) and mobile phase B (90% of 0.02% TFA in methanol and 10% of water) were used in gradient elution mode. A total of 75 μL of each solution was injected and peak responses were quantified at 220 nm. The method was found specific, precise, accurate, linear, rugged, robust and sensitive. During stability studies of fesoterodine fumarate extended-release tablets, one unknown impurity at relative retention time 1.37 was found increasing beyond the identification threshold. This impurity was isolated by using Preparative HPLC and structure was elucidated using mass and NMR spectroscopy. This method is a simple, inexpensive HPLC method that can be used as a routine quality control test for the estimation of impurities in fesoterodine fumarate extended-release tablets.

中文翻译：

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质谱指示兼容的流动相用于指示富马酸非索特罗定中过程相关的杂质和降解产物的稳定性指示RP-HPLC方法

摘要

本工作的目的是开发一种灵敏，选择性，准确和精确的稳定性指示HPLC方法，用于定量富马酸非索特罗定缓释片中的降解产物和过程相关杂质。通过进行强制降解研究，研究了降解情况，并分离了降解过程中形成的所有降解产物。使用保持在30°C的250×4.6 mm，5μm的Waters Symmetry C18色谱柱进行色谱分离。以梯度洗脱模式使用流动相A（在水中0.05％的三氟乙酸）和流动相B（在甲醇中的90％的0.02％TFA和10％的水）。总共注入75μL每种溶液，并在220 nm处定量峰响应。发现该方法特定，精确，准确，线性，坚固，鲁棒和灵敏。在非索罗定富马酸盐缓释片的稳定性研究中，发现在相对保留时间1.37处的一种未知杂质增加到超过鉴定阈值。通过使用制备型HPLC分离该杂质，并使用质谱和NMR光谱阐明结构。该方法是一种简单，廉价的HPLC方法，可用作常规质量控制测试，以评估富马酸非索特罗定缓释片中的杂质。