Effect of Organic Modifier on Elution Behavior of Voriconazole in Supercritical Fluid Chromatography: Development of Validated SFC Method

Background: Voriconazole (VORI), a derivative of fluconazole, shows a greater selectivity for the fungal enzyme than for the corresponding rat liver enzyme as compared to Ketoconazole and Itraconazole. Methods: An environment friendly, simple, rapid, and isocratic robust supercritical fluid chromatographic method has been developed and validated for determining Voriconazole (VORI) in Bulk drug and laboratory mixture representing the marketed dosage form. Efficient chromatographic separation was achieved on a SFC Packed Crest C18 T (150 4.0 mm, 5.0 μm) with mobile phase CO2, in isocratic combination with methanol (MeOH) 90: 10, respectively, at a flow rate of 1.0 mL/min; the eluent being monitored at 256 nm using UV-detector. The supercritical nature of carbon dioxide was maintained at 12 MPa pressure and 40°C temperature. Results: In the optimized method, the retention time of VORI was 3.5 minute. The test solution was found to be stable in the blank for 24 h. Robustness of the developed SFC method was optimized by varying chromatographic conditions viz. column oven temperature, flow rate, SFC temperature and pressure change. Conclusion: Regression analyses indicate correlation coefficient value greater than 0.997 for VORI in the linearity range of 100-400 μg/mL. The method had shown good, consistent recoveries for VORI (99.3-101.2%). The method was found to be accurate, precise, linear, specific, sensitive, rugged and robust.