Preparation and characterization of two new forced degradation products of letrozole and development of a stability-indicating RP-LC method for its determination

ABSTRACT

Two new hydrolytic products of letrozole were identified and proved to be true degradation products obtained by alkaline and acidic degradation of the drug. The acid and amide forms of the nitrile groups of letrozole were prepared and identified by IR and mass spectroscopic techniques. Subsequently, a simple, precise and selective stability-indicating RPLC method was developed and validated for the determination of letrozole in the presence of its degradation products. Letrozole was subjected to alkali and acid hydrolysis, oxidation, thermal degradation and photo-degradation. The degradation products were well isolated from letrozole. The chromatographic method was achieved usinggradient elution of the drug and its degradation products on a reversed phase Zorbax Eclipse C18 column [100mm x 4.6mm, 3.5microm] using a mobile phase consisting of 0.01M KH[2]PO[4] and methanol at a flow rate of 1mL min[?1]. Quantitation was achieved with UV detection at 230nm. Linearity, accuracy and precision were found to be acceptable over the concentration range of 0.01-80microgmL[-1]. The proposed method was successfully applied to the determination of letrozole in bulk, plasma and in its pharmaceutical preparation