A VALIDATED STABILITY-INDICATING RP-LC METHOD FOR PROPYLTHIOURACIL WITH LC-MS STUDIES OF FORCED DEGRADATION PRODUCTS AND SIMULTANEOUS ESTIMATION OF ITS IMPURITY

A simple, precise, accurate, sensitive and robust stability-indicating HPLC method for simultaneous estimation of propylthiouracil and its impurity thiourea has been proposed. The separation was achieved on a C₁₈ column (4.6 mm × 150 mm, particle size 5.0 μm) maintained at 45 ºC with a mobile phase composed of water: methanol: acetonitrile (50:35:15 v/v/v) with 0.1% acetic acid and detection wavelength was 241 nm. In statistical analysis, the linear response in the range of 30 – 300 μg/ml for propylthiouracil and 0.3 – 30 μg/ml for thiourea with a correlation coefficient greater than 0.99 was obtained. In forced degradation studies, PTU was found to degrade under basic hydrolysis, oxidative and photo stress while found resistant to acid/neutral hydrolysis and thermal degradation. The probable structures of six major degradants generated under stress conditions were identified by LC-MS studies and the most likely degradation pathway was proposed from mass spectral data. The information presented herein could be very useful for the impurity profiling of drugs as well as can be employed to check the drug product quality during stability studies.