A validated stability-indicating LC method for the separation of enantiomer and potential impurities of Linezolid using polar organic mode

Abstract

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.

Simultaneous determination and stability studies of linezolid, meropenem and vancomycin in bacterial growth medium by high-performance liquid chromatography

“…LZD displayed a favourable stability profile and did not degrade under the experimental conditions of the in vitro infection model. This is in agreement with previous results for MHB from Scheerans et al [6] and Schmidt et al [18] or under yet more stressed conditions (LZD in aqueous solution at 70° C for 48 h) described by Raju and co-workers [19] who also found no significant degradation of LZD. For VAN, minor degradation to 90.6% of the initial concentration was observed within 24 h which is still considered stable by the EMA guideline [15].…”

Smart Methods for Linezolid Determination in the Presence of Alkaline and Oxidative Degradation Products Utilizing Their Overlapped Spectral Bands

“…IR and MS analyses of LIN degradation products showed that the drug undergoes degradation under alkaline conditions through hydrolysis of the amide linkage producing ALK as suggested by Lopes and Salgado [8]. The N-oxide of the morpholine moiety in LIN structure was suggested as the oxidative degradation product via oxidation producing OXD on the basis of the studies of S. Raju et al [24].…”