Kondra Sudhakar Babu, Madireddy Venkataramanna, Chilukuri Mohanareddy, Papadasu Narayanareddy, Jonnalagadda Latha
Department of Chemistry, Sri Krishna Devaraya University, Anantapur 515003, India.
Department of Chemistry, Sri Krishna Devaraya University, Anantapur 515003, India Hetero Labs Limited, Hetero House, Sanathnagar, Hyderabad 500078, India
J Chromatogr Sci. 2014 Sep;52(8):880-5. doi: 10.1093/chromsci/bmt134. Epub 2013 Sep 12.
A novel stability-indicating ultra performance liquid chromatographic (UPLC) method has been developed for quantitative determination of nilotinib hydrochloride in active pharmaceutical ingredients along with four impurities (imp-1, imp-2, imp-3 and imp-4). The method is applicable to the quantification of related compounds and assay of nilotinib hydrochloride drug. Efficient chromatographic separation was achieved on a Shim-pack XR-ODS II, 75 × 3.0 mm, 1.8-µm column with a gradient mobile phase combination. Quantification was carried at 260 nm at a flow rate of 0.6 mL min(-1). Stress degradation conditions were established for nilotinib hydrochloride by subjecting it to acid, base, oxidation, humidity, thermal and photolysis. The stress samples were assayed against a qualified reference standard and the mass balance was found close to 97.0%. The developed UPLC method was validated according to the present International Conference on Harmonisation guidelines for specificity, detection limit, quantitation limit, linearity, accuracy, precision, intermediate precision and robustness. The resolution between nilotinib hydrochloride and four potential impurities is found to be >2.0. Regression analysis shows as r value (correlation coefficient) of >0.999 for nilotinib hydrochloride and four potential impurities.
已开发出一种新型的稳定性指示超高效液相色谱（UPLC）方法，用于定量测定活性药物成分中的盐酸尼罗替尼以及四种杂质（杂质-1、杂质-2、杂质-3和杂质-4）。该方法适用于盐酸尼罗替尼相关化合物的定量分析和含量测定。采用梯度流动相组合，在Shim-pack XR-ODS II，75×3.0 mm，1.8-µm色谱柱上实现了高效的色谱分离。在260 nm波长、0.6 mL min(-1)的流速下进行定量分析。通过对盐酸尼罗替尼进行酸、碱、氧化、湿度、热和光解处理，建立了其强制降解条件。将强制降解样品与合格的参考标准品进行测定，质量平衡接近97.0%。根据现行国际协调会议指南，对所开发的UPLC方法进行了专属性、检测限、定量限、线性、准确度、精密度、中间精密度和稳健性的验证。盐酸尼罗替尼与四种潜在杂质之间的分离度大于2.0。回归分析表明，盐酸尼罗替尼和四种潜在杂质的r值（相关系数）大于0.999。
