Development of a new stability indicating method for the simultaneous separation of voriconazole from its impurities along with sodium benzoate used as a preservative in a powder for oral suspension

Abstract

Voriconazole is a second-generation triazole derived from fluconazole, having an enhanced antifungal spectrum, compared with older triazoles. It is the drug of choice for treatment of invasive aspergillosis and many Scedosporium/Pseudallescheria Fusarium infections. Voriconazole is available in both intravenous and oral formulations. Since there is much interest in pharmaceutical quality control, separation of impurities from the main drug substances and accurate assay quantification, and since there is no reference or monograph until nowadays reported for the simultaneous separation of voriconazole from its specified and unspecified impurities along with sodium benzoate used as an antimicrobial preservative, our aim of this work is to develop a new simple, sensitive and stability indicating assay method allowing thus separation by high-performance liquid chromatography. The development of our method consisted in optimizing the following analytical parameters: nature and composition of the mobile phase, its pH, buffer concentration, nature of the stationary phase, column temperature and detection wavelength. After optimisation, separation was achieved on a stainless steel column NOVAPACK C18 (3.9mm×150mm; 4μm particle size) using a gradient mode with methanol, acetonitrile R and an aqueous solution acidified by acetic acid at 1% and adjusted to pH 2.77. The eluted compounds were monitored at 254nm. The flow rate was set at 1.0mL/min, the injection volume at 10μL, and the column oven temperature was maintained at 35°C. Under these conditions, separation was achieved with good resolution and symmetrical peaks' shape. The developed method was validated according to the International Conference on Harmonization (ICH) guidelines, and then it was successfully applied to establish inherent stability of the pharmaceutical formulation subjected to different ICH prescribed stress conditions. The developed method was proved to be simple, specific and precise. Hence, it can be considered as a method for stability study and for routine quality control analysis of voriconazole and sodium benzoate in a powder for oral suspension.

Keywords: Benzoate de sodium; Chromatographie liquide; Degradation products; Dégradation forcée; Liquid chromatography; Produits de dégradation; Sodium benzoate; Stress studies; Voriconazole.