Enantiomeric separation of several antimycotic azole drugs using supercritical fluid chromatography

Abstract

The chiral resolution of four antifungal compounds, three imidazoles (miconazole, econazole and sulconazole) and one triazole (itraconazole) using supercritical fluid chromatography on the amylose-based chiral stationary phase Chiralpak AD, is presented in this work. The influence of pressure, type and percentage of organic modifier and temperature on retention times and resolution was studied. The enantiomeric separation of the three imidazoles was achieved with resolutions higher than two and analysis times lower than 10 min, obtaining the best results using methanol as modifier. However, the analysis time of the triazole was higher than 80 min due to the existence of a high number of functional groups that were able to interact with the chiral stationary phase. In this case, the resolution of the four stereoisomers was achieved only partially with mixtures of ethanol and 2-propanol as modifier. The isoenantioselective temperatures were obtained from the study of the influence of the temperature, they were above the range of temperatures assayed, except for sulconazole using 2-propanol.