Satyanarayana Raju T, Vishweshwari Kutty O, Ganesh V, Yadagiri Swamy P
Dr. Reddy's Laboratories Ltd. Active Pharmaceutical Ingredients, IPDO, Bachupally, Hyderabad 500072, A.P, India.
Department of Chemistry, University College of Engineering, Osmania University, Hyderabad 500007, India.
J Pharm Anal. 2012 Aug;2(4):272-278. doi: 10.1016/j.jpha.2012.03.006. Epub 2012 Mar 18.
Although a number of methods are available for evaluating Linezolid and its possible impurities, a common method for separation if its potential impurities, degradants and enantiomer in a single method with good efficiency remain unavailable. With the objective of developing an advanced method with shorter runtimes, a simple, precise, accurate stability-indicating LC method was developed for the determination of purity of Linezolid drug substance and drug products in bulk samples and pharmaceutical dosage forms in the presence of its impurities and degradation products. This method is capable of separating all the related substances of Linezolid along with the chiral impurity. This method can also be used for the estimation of assay of Linezolid in drug substance as well as in drug product. The method was developed using Chiralpak IA (250 mm×4.6 mm, 5 μm) column. A mixture of acetonitrile, ethanol, n-butyl amine and trifluoro acetic acid in 96:4:0.10:0.16 (v/v/v/v) ratio was used as a mobile phase. The eluted compounds were monitored at 254 nm. Linezolid was subjected to the stress conditions of oxidative, acid, base, hydrolytic, thermal and photolytic degradation. The degradation products were well resolved from main peak and its impurities, proving the stability-indicating power of the method. The developed method was validated as per International Conference on Harmonization (ICH) guidelines with respect to specificity, limit of detection, limit of quantification, precision, linearity, accuracy, robustness and system suitability.
虽然有多种方法可用于评估利奈唑胺及其可能的杂质，但目前仍没有一种能高效地同时分离其潜在杂质、降解产物和对映体的通用方法。为了开发一种运行时间更短的先进方法，我们开发了一种简单、精确、准确的稳定性指示液相色谱法，用于测定原料药及制剂中利奈唑胺的纯度，该方法可在杂质和降解产物存在的情况下进行测定。该方法能够分离利奈唑胺的所有相关物质以及手性杂质。该方法还可用于测定原料药和制剂中利奈唑胺的含量。该方法采用Chiralpak IA（250 mm×4.6 mm，5μm）色谱柱进行开发。以体积比为96:4:0.10:0.16（v/v/v/v）的乙腈、乙醇、正丁胺和三氟乙酸的混合物作为流动相。在254 nm波长处监测洗脱的化合物。利奈唑胺分别进行了氧化、酸、碱、水解、热和光解降解等强制降解试验。降解产物与主峰及其杂质得到了很好的分离，证明了该方法的稳定性指示能力。按照国际协调会议（ICH）指南对所开发的方法进行了特异性、检测限、定量限、精密度、线性、准确度、耐用性和系统适用性等方面的验证。
