A stability-indicating gradient reverse-phase liquid chromatographic method was developed for the quantitative determination of process-related impurities and forced degradation products of oxcarbazepine in pharmaceutical formulation. The method was developed by using Inertsil cyano (250 × 4.6 mm) 5 μm column with mobile phase containing a gradient mixture of solvent A (0.01 M sodium dihydrogen phosphate, pH adjusted to 2.7 with orthophosphoric acid and acetonitrile in the ratio of 80:20 v/v) and B (50:40:10 v/v/v mixture of acetonitrile, water, and methanol). The flow rate of mobile phase was 1.0 mL min−1. Column temperature was maintained at 25°C and detection wavelength at 220 nm. Developed reverse-phase high-performance liquid chromatography (RP-HPLC) method can adequately separate and quantitate five impurities of oxcarbazepine, namely imp-A, imp-B, imp-C, imp-D, and imp-E. Oxcarbazepine was subjected to the stress conditions of oxidative, acid, base, hydrolytic, thermal, and photolytic degradation. Oxcarbazepine was found to degrade significantly in acid, base, and oxidative stress conditions. The degradation products were well resolved from oxcarbazepine and its impurities. The developed method was validated as per International Conference on Harmonization (ICH) guidelines with respect to specificity, linearity, limit of detection and quantification, accuracy, precision, and robustness.
Authors:N. Kumar, D. Sangeetha, R. Goyal, and P. S. Reddy
A simple, selective, and stability-indicating reverse phase liquid chromatographic method has been developed and validated for the simultaneous determination of impurities and forced degradation products of quetiapine fumarate. The chromatographic separation was achieved on Inertsil-3 C8, 150 mm × 4.6 mm, 5 μm column at 35°C with UV detection at 217 nm using gradient mobile phase at a flow rate of 1.0 mL/min. Mobile phase A contains a mixture of 0.01 M di-potassium hydrogen orthophosphate (pH 6.8) and acetonitrile in the ratio of 80:20 (v/v), respectively, and mobile phase B contains a mixture of 0.01 M di-potassium hydrogen orthophosphate (pH 6.8) and acetonitrile in the ratio of 20:80 (v/v), respectively. The drug product was subjected to the stress conditions of oxidative, hydrolysis (acid and base), hydrolytic, thermal, and photolytic degradation. Quetiapine fumarate was found to degrade significantly in acid, base, and oxidative stress conditions. The degradation products were well resolved from main peak and its impurities. The mass balance was found to be in the range of 96.6–102.2% in all the stressed conditions, thus proved the stability-indicating power of the method. The developed method was validated as per ICH guidelines with respect to specificity, linearity, limit of detection and quantification, accuracy, precision, and robustness.
Authors:M. Vamsi Krishna, R. N. Dash, B. Jalachandra Reddy, P. Venugopal, P. Sandeep, and G. Madhavi
An isocratic ion-pair reversed phase high-performance liquid chromatography-ultraviolet (RP-HPLC-UV) method for analysis of eberconazole nitrate in bulk and in pharmaceutical dosage forms has been developed and validated. Best separation was achieved on Lichrospher C18 column (250 mm × 4.6 mm, 5 μm) using a mobile phase of 10 mM potassium dihydrogen phosphate containing 10 mM tetra-butyl ammonium hydroxide (pH adjusted to 2.8 with ortho phosphoric acid) and methanol (75:25, v/v) at a flow rate of 1.0 mL min−1. UV detection was performed at 220 nm. The method was validated for specificity, linearity, precision, accuracy, limit of detection, limit of quantification, robustness, and solution stability. The calibration plot was linear over the concentration range of 10–80 μg mL−1 (r2 = 0.999) and the limits of detection and quantification were 0.3 and 0.9 μg mL−1, respectively. Intra-day and inter-day precisions were 1.13% and 1.67%, respectively. Experimental design was employed to optimize the method. The method was successfully used for analysis of eberconazole nitrate in commercially available cream (Ebernet).