Separation and estimation of process related impurities and degradation products of levetiracetam in solid pharmaceutical formulation using ion-pair chromatography

摘要

A stability-indicating ion-pair chromatographic method was developed and validated for the simultaneous estimation of impurities and forced degradation products of levetiracetam in tablet formulation. The chromatographic separation was achieved on ACE C8 (150 mm × 4.6 mm I.D., 5 μm) column at 25°C with UV detection at 200 nm using an isocratic mobile phase at a flow rate of 0.9 mL/min. Mobile phase contains a mixture of buffer (50 mM sodium di-hydrogen orthophosphate and 1.25 mM sodium 1-octanesulfonate monohydrate, pH adjusted to 2.6 with orthophosphoric acid) and acetonitrile in the ratio of 95:5 (v/v), respectively. The drug product was exposed to the stress conditions of oxidative, hydrolysis (acid and base), hydrolytic, thermal, and photolytic degradation. Significant degradation was observed during acid, base hydrolysis, and oxidative stress conditions. The degradation products were well-resolved from the main peak and its impurities; and the peak purity for the levetiracetam peak was passed in all stress samples. The mass balance was found to be in the range of 98.1-101.7% in all the stressed conditions, thus proving 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.