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.

Quantitative determination of voriconazole by thionine reduction and its potential application in a pharmaceutical and clinical setting

“…The obtained LOD and LOQ make this method promisingly comparable to those described in the literature for UV spectrophotometry, and therefore implies that it would be appropriate for routine determinations regarding its clinical use. [34][35][36] Additionally, solution-state NMR analyses of VCZ degradation under alkaline conditions agreed with previous studies. But interestingly, the nding and structure elucidation of a new and not previously described VCZ DP, named DP3 aer previous VCZ decomposition products, is reported for the rst time.…”

Assessment of greenness for the determination of voriconazole in reported analytical methods

“…The remaining methods have utilized a common organic solvent such as ACN and MeOH along with a solid buffer. The different buffers used for the reported methods were phosphate with the corresponding salts of ammonium, 79 sodium, 81,82,84 and potassium, 86 which produced similar results in the greenness assessment.…”

Enhanced Aerosolization of High Potency Nanoaggregates of Voriconazole by Dry Powder Inhalation

“…FTIR was used to study chemical interactions between voriconazole and mannitol. The hydroxyl group of voriconazole is related to its degradation pathway, 40 and it could be the most active site if there are any intermolecular interactions. If this occurred, this would shift the FT-IR peaks of voriconazole ranging between 3100 and 3500 cm −1 .…”