Optimisation and validation of a fast HPLC method for the quantification of sulindac and its related impurities.

Fabrice Krier, Michaël Brion, Benjamin Debrus, Pierre Lebrun, Aurélie Driesen, Eric Ziemons, Brigitte Evrard, Philippe Hubert

Index: J. Pharm. Biomed. Anal. 54(4) , 694-700, (2011)

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Abstract

The European Pharmacopoeia describes a liquid chromatography (LC) method for the quantification of sulindac, using a quaternary mobile phase including chloroform and with a rather long run time. In the present study, a new method using a short sub-2 μm column, which can be used on a classical HPLC system, was developed. The new LC conditions (without chloroform) were optimised by means of a new methodology based on design of experiments in order to obtain an optimal separation. Four factors were studied: the duration of the initial isocratic step, the percentage of organic modifier at the beginning of the gradient, the percentage of organic modifier at the end of the gradient and the gradient time. The optimal condition allows the separation of sulindac and of its 3 related impurities in 6 min instead of 18 min. Finally, the method was successfully validated using an accuracy profile approach in order to demonstrate its ability to accurately quantify these compounds.Copyright © 2010 Elsevier B.V. All rights reserved.