SEPARATION AND PURIFICATION OF VORICONAZOLE ENANTIOMER BY SUPERCRITICAL FLUID CHROMATOGRAPHY

Abstract

The present research work involves the development and purification of a novel supercritical fluid chromatography SFC) method for the separation of voriconazole and its enantiomer. The separation of the aforementioned compounds was examined using ten different polysaccharide derivatives of the amylose and cellulose columns, solvents having a broad range of polarities such as methanol, acetonitrile, 2-propanol, ethanol. The effect of both acidic (TFA) and basic (DEA) additives (0.1-0.5% v/v) was also tried to achieve better separation. Elution times and enantio-selectivities of above mentioned conditions affected the separation of the drug and its enantiomer. Finally, the chromatographic conditions have been fully optimized to achieve the excellent separation of these compounds. Voriconazole and its enantiomer were well separated with the resolution of 5.4 on an amylose derivative of the Chiralpak AD-H column (250x4.6 mm, 5µ), backpressure 100 bar, within 10 min of runtime using supercritical fluid chromatography (SFC). The method developed has been applied for separating the desired voriconazole and its enantiomer. In addition, it is also used for the isolation and purification of voriconazole between mg to g level. Thus, the method developed was quick and easy to apply from an analytical scale to a preparative scale.