Identification of Major Degradation products of Ketoconazole

Rajendra A Mhaske

doi:10.3797/scipharm.1107-18

Abstract

Analytical methods were developed for the identification of major degradation products of Ketoconazole, an antifungal agent. The stressed degradation of Ketoconazole drug substance was performed under acid, base, thermal, photo and oxidative stress conditions. The major degradation was observed under acid, base and oxidative stress conditions. The degradation study was performed on Inertsil ODS-3V, length 100 X diameter 4.6 mm, particle size 3 μm column using gradient method. These degradants were identified by LC-MS technique.

Highlights

Ketoconazole is an antifungal drug approved by the US FDA in 1981
One is hydrolysis product of Ketoconazole observed under acid/ base condition and the other one is oxidative degradent observed under oxidative stress condition
The identification of oxidative degradent was achieved by LC-MS, NMR and Elemental analysis

Summary

Introduction

Ketoconazole is an antifungal drug approved by the US FDA in 1981. Only a few analytical methods for the determination of the drug in biological samples and in the presence of other drugs have been reported [1–12]. The present study deals with understanding the degradation behavior of Ketoconazole by subjecting it to acid, base, aqueous, thermal, photo and oxidative stress conditions. One unknown degradation impurity was observed under acidic condition (Table 3 and figure 1c). Sample heated on boiling water bath for 10 min and 30 min, respectively, neutralized with 1N HCl solution and make up the volume to 25 ml with methanol.

Results

Conclusion