AN EXPERIMENTAL DESIGN APPROACH FOR THE FORCED DEGRADATION STUDIES AND DEVELOPMENT OF A STABILITY-INDICATING LC METHOD FOR EPLERENONE IN TABLETS

Abstract

A stability-indicating liquid chromatographic (LC) method was developed and validated for quantitative determination of eplerenone in tablets. Eplerenone (drug and drug product) solutions were exposed to acid, alkali, and water hydrolysis; oxidation by hydrogen peroxide; thermal stress; and photolytic conditions to evaluate the stability-indicating nature of the method. An experimental design was used during the forced degradation and the factors and/or combination of factors that were most likely to affect degradation of eplerenone were identified using multiple regression and Yates analysis. The chromatographic method employed a HiQ sil C-18HS (250 × 4.6 mm, 5 µm) column with mobile phase consisting of methanol and water (70:30, v/v). The detection was done at 241 nm. The procedure was validated for linearity, accuracy, precision, and specificity. There was no interference of excipients and degradation products in the determination of active pharmaceutical ingredient. The method showed good accuracy and precision (intra- and inter-day), and the response was linear over a range from 2 to 20 µg/mL. All the degradation products were characterized through LC-MS analysis and the study of mass fragmentation pattern. The method was found to be simple and fast with less trial and error experimentation by making use of experimental design.

Keywords:

• eplerenone
• experimental design
• LC-MS
• multiple regression
• stability-indicating method

ACKNOWLEDGMENTS

Authors are thankful the trustees of Bhujbal Knowledge City, Nashik for providing necessary analytical facilities to carry out this work and Hetero Drug Laboratories, Hyderabad (INDIA) for providing gift sample of eplerenone.

Notes

*WMS: Within Mean Square;.

^#BMS: Between Mean Square.