Isolation, Purification and Structural Identification of Degradation Products from Ketoconazole in a Liquid Formulation: An HPLC and HPLC-MS/MS Study

Zhang Fa

doi:10.36959/326/767

Abstract

Ketoconazole is the active ingredient in an antifungal liquid formulation for topical application. A binary gradient HPLC analysis indicated that ketoconazole in the formulation produced four degradation products at minor levels after storage at room temperature for about 3 years.

Highlights

Ketoconazole (cis-1-acetyl-4-[4-[[2-(2,4-dichlorophenyl)2-(1H-imidazole-1-ylmethyl)-1,3-dioxolan-4-yl]-methoxy] phenyl]piperazine) (I) (Scheme I) is an imidazole antifungal reagent
Peak I is due to ketoconazole and at least four suspected degradation products were observed, which were labeled as II, III, IV and V, respectively
Based on the comparison between the structures of ketoconazole and that of degradation products II, III, IV, and V, it is concluded that II might be formed from hydrolysis of ketoconazole

Summary

Introduction

Ketoconazole (cis-1-acetyl-4-[4-[[2-(2,4-dichlorophenyl)2-(1H-imidazole-1-ylmethyl)-1,3-dioxolan-4-yl]-methoxy] phenyl]piperazine) (I) (Scheme I) is an imidazole antifungal reagent. Degradation of ketoconazole in this formulation after storage at room temperature for about three years was studied. Four degradation products (II, III, IV and V) (Scheme I) at minor levels were detected, isolated and purified using reversed-phase high performance liquid chromatographic methods.

Results

Conclusion