HPLC Methods for Stress Testing of ZL-S Drug Substances

Ewelina Czerniec-Michalik ,  Maria Puchalska ,  Tatyana Gilevska ,  Magdalena Kossykowska ,  Katarzyna Badowska-Rosłonek 

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

Abstract

ZL-S, namely the 4-({3-[2-(dimethylamino)ethyl]-1H-indol-5-yl}- methyl)-1,3-oxazolidin-2-one is very potent serotonine receptor inhibitor. The primary objectivev ot this research was to study the degradation behaviour of ZL-S under different stress conditions by HPLC with UV detection and to establish stability of this drug substance. The secondary was to establish the stability indicating HPLC methods for assessment of purity and content of ZL-S.

ZL-S was exposed to the recommended by Internetional Conference of Charmonisation stress conditions. The alkaline and acidic hydrolysis, oxidation, photolysis and thermal decomposition stress tests were applied. Almost total degradation  occurred in alkaline medium. Partial degradation was observed under oxidative stress conditions, in the acidic medium and in the neutral conditions. The investigated substance was stable under thermal and photo stress conditions.

Satisfying separation of API from degradants formed during stress tests was achieved on a C-18 column using phosphate buffer and acetonitrile as the mobile phase in a gradient mode. Paralelly, the assay of ZL-S was determined in the same chromatographic conditions.

In order to establish the enantiomeric purity of both, ZL-S before and after the stress tests, the separation of drug from its isomer (D) and degradation products was carried out on a Chiralpak AD-H column using a mobile phase consisting of n-hexane, isopropanol, metanol, diethylamine.

Analytical methods used in the stress testing experiments were validated with respect to specifity, linearity, precision, accuracy and robustness. The efficiency of the procedure was verified by its application to standards of potential impurities which emerged in course of the synthesis. The products formed during the stress studies were similar to standards produced by Chemistry Department of Pharmaceutical Research Institute.

 

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Presentation: Poster at VII Multidyscyplinarna Konferencja Nauki o Leku, by Ewelina Czerniec-Michalik
See On-line Journal of VII Multidyscyplinarna Konferencja Nauki o Leku

Submitted: 2010-03-15 09:50
Revised:   2010-04-21 15:35