Enantiomeric Separation of Linezolid by Chiral Reversed-Phase Liquid Chromatography

Abstract

A chiral liquid chromatographic method is developed for the enantiomeric resolution of Linezolid, (S)(-)-N-[[-3-(3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl] methyl] acetamide, an antibiotic in bulk drugs. The enantiomers of Linezolid are resolved on a Chiralcel OJ-RH column using a mobile phase system containing 150mM di-sodium hydrogen phosphate buffer (pH 4.5)-acetonitrile (86:14, v/v). The resolution between the enantiomers is found to be two. The developed method is extensively validated and proved to be robust. The limit of detection and limit of quantification of (R)-enantiomers are found to be 94 and 375 ng/mL, respectively, for 10 microL injection volume. The percentage recovery of (R)-enantiomer is ranged from 98.9 to 102.9 in bulk drug samples of Linezolid. Linezolid sample solution and mobile phase are found to be stable for at least 48 h. The proposed method is found to be suitable and accurate for the quantitative determination of (R)-enantiomer in bulk drugs.

Liquid chromatographic separation and thermodynamic investigation of lorcaserin hydrochloride enantiomers on immobilized amylose–based chiral stationary phase

“…The equilibrium binding constant ( k i ) that measures the binding strength may be based on standard Gibbs free energy change (ΔG): where R is the universal gas constant (8.3144 J/[mol·K]), T is the absolute temperature in Kelvin, k i is the binding constant, and i denotes the corresponding enantiomers. The large energy difference is set free upon solute and CSP association; because of favorable energetic state of bound versus free solute, this will give large association constant …”

“…The large energy difference is set free upon solute and CSP association; because of favorable energetic state of bound versus free solute, this will give large association constant. [18][19][20] The Gibbs free energy is composed of enthalpic and entropic contributions (ΔH°and ΔS°), the enantiomeric strong binding driven by intermolecular interaction as measured by the enthalpy change ΔH. The process of complexation is usually paid off by an entropic cost ΔS, shown as following Gibbs-Helmholtz equation:…”

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

“…In the literature a number of methods have been described for the determination of Linezolid and its impurities employing various techniques such as HPLC [4] , [5] , [6] , [7] , [8] , [9] , [10] , [11] , chiral HPLC [12] , [13] , [14] , capillary electrophoresis [15] , [16] , [17] , [18] and NMR [19] . The major objective of the present work is to develop a single method for the separation of chiral and nonchiral impurities of Linezolid in drug substance and drug product and also the method should have low LOD and LOQ values.…”

Racemic drug resolution: a comprehensive guide

“…b-blockers), 3,[261][262][263] albuterol (salbutemol), terbutaline (b 2 -adrenoceptor agonists i.e. bronchodilators), 264,265 linezolid (antibiotic), [266][267][268] and rolipram (antiinammatory) 269 ¼ d-(+)-inactive, l-(À)-active…”