Optimisation and validation of a fast HPLC method for the quantification of sulindac and its related impurities.
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.
Laboratory of Pharmaceutical Technology, Department of Pharmacy, CIRM, University of Liège, Av. de l'Hôpital 1, Liège, Belgium. Fabrice.Krier@ulg.ac.be
Fabrice
F
Krier
Michaël
M
Brion
Benjamin
B
Debrus
Pierre
P
Lebrun
Aurélie
A
Driesen
Eric
E
Ziemons
Brigitte
B
Evrard
Philippe
P
Hubert
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000032:analysis*; D002851:Chromatography, High Pressure Liquid; D004340:Drug Contamination / Q000517:prevention & control; D055772:Green Chemistry Technology; D007536:Isomerism; D057230:Limit of Detection; D008956:Models, Chemical; D015233:Models, Statistical; D009010:Monte Carlo Method; D011786:Quality Control; D015203:Reproducibility of Results; D012997:Solvents; D013467:Sulindac / Q000031:analogs & derivatives / Q000032:analysis*; D013678:Technology, Pharmaceutical; D013997:Time Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D012997:Solvents; D013467:Sulindac; C025462:sulindac sulfide; C025463:sulindac sulfone