A validated stability-indicating liquid chromatographic method for determination of degradation impurities and diastereomers in voriconazole tablets

Abstract

A reversed-phase gradient liquid chromatographic method has been developed for the quantitative determination of Voriconazole, along with its degradation and diastereomeric impurities in tablet dosage form. Chromatographic separation has been achieved on an Inertsil ODS 3V, 150 × 4.6 mm, 5 μm column. The mobile phase consisting of solvent A 0.05 molar (M) potassium dihydrogen phosphate (pH 2.5 buffer) and solvent B (mixture of acetonitrile and methanol in the ratio 90:10 (v/v)), was delivered at a flow rate of 1.2 mL min-1 with the detection wavelength at 256 nm. Resolution of Voriconazole and all five potential impurities was achieved at greater than 2.0 for all pairs of compounds. The drug was subjected to stress conditions such as oxidative, acid and base hydrolysis, and thermal and photolytic degradation. Voriconazole was found to degrade significantly under base hydrolysis stress conditions compared to acid hydrolysis stress conditions. The degradation products were well-resolved from the main peak and its impurities, thus proving the stability-indicating power of the method. The stressed samples were assayed against a reference standard and the mass balance was found to be close to 99.0%. The developed method was validated as per ICH guidelines with respect to specificity, linearity, limit of detection, limit of quantification, accuracy, precision, and robustness. © Shaikh and Patil.