Validation of a HPLC method for LI-S analysis

Marta Zezula ,  Maria Puchalska ,  Magdalena Kossykowska ,  Aleksandra Groman ,  Agata E. Kamieńska-Duda ,  Wojciech J. Szczepek 

Pharmaceutical Research Institute (IF), Rydygiera 8, Warszawa 01-793, Poland

Abstract

A new liquid chromatography method has been developed and validated for the analysis of LI-S ((5R)-N-{[3-(3-fluoro-4 -morpholinylphenyl) -2-oxo-5-oxazolidynyl] methyl}acetamide)  (Fig.1) and its impurities L7 ((5R)-[3-(3-fluoro-4 -morpholinylphenyl) -2-oxo-5-oxazolidynyl] methanol) and L9 ((5R)-[3-(3-fluoro-4-morpholinylphenyl) -2-oxo-5-oxazolidynyl] metyl azide).

lis3.gif

Fig. 1 Molecular structure of LI-S

The separation was achieved on a C18 column with a mobile phase consisted potassium phosphate dibasic buffer, and acetonitrile. In the course of research its was found that the separation between LI-S and L7 is a critical parameter, and its value should be higher than 1.5.

Validation of the method included: selectivity, specificity, method precision, intermediate precision, accuracy (recovery), linearity, limits of detection and quantitation (LOD and LOQ), robustness. The selectivity of the method for chemical impurities determination was demonstrated for 3 analytes: LI-S, L7 (RRT 0.9) and L9 (RRT 2.9). 
The method for chemical impurities determination was found to be linear (with an R2 value of 0.999) and precise (with and RSD value of 1.4 %). The LOQ and LOD for LI-S and its chemical impurities were calculated and were found to be 0.01 % and 0.007 % respectively.

The developed and validated method meets the EP criteria of acceptance.

 

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Presentation: Poster at VII Multidyscyplinarna Konferencja Nauki o Leku, by Marta Zezula
See On-line Journal of VII Multidyscyplinarna Konferencja Nauki o Leku

Submitted: 2010-03-15 09:40
Revised:   2010-04-07 13:23