Development of validated stability-indicating chromatographic method for the determination of fexofenadine hydrochloride and its related impurities in pharmaceutical tablets.
Development of validated stability-indicating chromatographic method for the determination of fexofenadine hydrochloride and its related impurities in pharmaceutical tablets.
复制标题
DOI：
10.1186/1752-153x-5-76
复制
发表时间：
2011-12-03
影响因子：
--
通讯作者：
Olah IV
中科院分区：
文献类型：
--
作者：
Maher HM;Sultan MA;Olah IV
开发了一种简单的反相高效液相色谱-二极管阵列检测器（HPLC-DAD）方法，随后验证了该方法用于测定盐酸非索非那定（FEX）及其有关化合物;酮非索非那定（杂质A）、非索非那定的Meta异构体（杂质B）、非索非那定的甲酯（杂质C）以及酮非索非那定的甲酯（杂质D）。分离基于使用Hypersil BDS C-18分析柱（250 × 4.6 mm，内径，5 μm）。移动的相由含有0.1gm %一水辛烷磺酸钠盐和1%（v/v）三乙胺的磷酸盐缓冲液（pH 2.7）和甲醇（60：40，v/v）的混合物组成。以赖诺普利为内标物，在215 nm波长处进行定量，线性范围为0.1 ~ 50 μg/ml。采用优化的条件建立了一种稳定性指示HPLC-DAD法，用于片剂中FEX及其有关物质的定量测定。药物经过氧化、水解、光解和加热以施加强制降解条件。实现了母体化合物和所有降解产物的完全分离。根据ICH指导原则，对该方法的准确度、精密度、耐用性、检测限和定量限以及分析验证的其他方面进行了验证。
A simple reversed phase high performance liquid chromatographic method with diode array detector (HPLC-DAD) has been developed and subsequently validated for the determination of fexofenadine hydrochloride (FEX) and its related compounds; keto fexofenadine (Impurity A), meta isomer of fexofenadine (Impurity B), methyl ester of fexofenadine (Impurity C) in addition to the methyl ester of ketofexofenadine (Impurity D). The separation was based on the use of a Hypersil BDS C-18 analytical column (250 × 4.6 mm, i.d., 5 μm). The mobile phase consisted of a mixture of phosphate buffer containing 0.1 gm% of 1-octane sulphonic acid sodium salt monohydrate and 1% (v/v) of triethylamine, pH 2.7 and methanol (60:40, v/v). The separation was carried out at ambient temperature with a flow rate of 1.5 ml/min. Quantitation was achieved with UV detection at 215 nm using lisinopril as internal standard, with linear calibration curves at concentration ranges 0.1-50 μg/ml for FEX and its related compounds. The optimized conditions were used to develop a stability-indicating HPLC-DAD method for the quantitative determination of FEX and its related compounds in tablet dosage forms. The drugs were subjected to oxidation, hydrolysis, photolysis and heat to apply stress conditions. Complete separation was achieved for the parent compounds and all degradation products. The method was validated according to ICH guidelines in terms of accuracy, precision, robustness, limits of detection and quantitation and other aspects of analytical validation.