Jayapalu Kalpana, Malipeddi Himaja
Acta Pol Pharm. 2017 Jan;74(1):81-92.
A rapid stability indicating liquid chromatography method was developed and validated for the simultaneous quantitation of related substances of antiretrovirals in combined oral dosage formulation. Separation was achieved using a Waters, Xterra RP-18 column (250 x 4.6 mm) with a mobile phase containing a gradient mixture of sodium acetate trihydrate solution and acetonitrile with a flow rate of 1 mL/min, detec- tion at 254 nm. A simple preparative and LC-MS method were applied for the isolation and identification of degradation products. The active drugs were subjected to stress studies and significant degradation was observed. The spectral purity of the active drugs was determined to establish the stability indicating power of the developed method. The developed chromatographic method was validated as per ICH guidelines and is capable to identify and quantify all the 17 impurities at a level of 0.01 and 0.03%, respectively, with respect to test concentration. The wide range of linearity and good resolution imply that the method is suitable for routine quantification of related substances as well as for the assay of the actives.
建立并验证了一种快速的稳定性指示液相色谱法，用于同时定量联合口服剂型中抗逆转录病毒药物的相关物质。使用 Waters Xterra RP - 18 柱（250×4.6 mm）进行分离，流动相为含有三水合醋酸钠溶液和乙腈的梯度混合物，流速为 1 mL/min，检测波长为 254 nm。采用简单的制备方法和液相色谱 - 质谱联用方法对降解产物进行分离和鉴定。对活性药物进行了强制降解试验，观察到明显的降解。测定活性药物的光谱纯度以确定所开发方法的稳定性指示能力。所开发的色谱方法按照国际协调会议（ICH）指南进行了验证，能够分别以相对于测试浓度 0.01%和 0.03%的水平鉴定和定量所有 17 种杂质。宽范围的线性和良好的分离度表明该方法适用于相关物质的常规定量以及活性成分的含量测定。
