A Validated Stability-Indicating RP-LC Method for the Estimation of Process-Related Impurities and Degradation Products of Quetiapine Fumarate in Solid Oral Dosage Form

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 x 4.6 mm, 5 mu m column at 35 degrees 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.