STABILITY INDICATING HPLC-MS/UV METHOD FOR DETERMINATION OF RACECADOTRIL FROM BULK AND FORMULATION

The present work was focused on the development of rapid, specific and novel stability indicating high performance liquid chromatographic method for determination of racecadotril (RAC) in bulk and capsule formulation. The drug and formulation were subjected to hydrolysis (acidic, alkaline and neutral), oxidative and thermal stress, as per ICH guidelines Q1A (R2). Degradation products of RAC formed under various stress conditions were well separated using a mobile phase containing acetonitrile and water (60:40 V/V) with 0.5% formic acid. Quantification was performed using RP C18 column with the detection wavelength of 230 nm.The method was considered linear in the concentration range of 5-100 μg mL−1 for RAC. Limit of detection and quantitation was found to be 0.15 and 0.45 μg mL−1 respectively. Identification of major stress degradation products was performed using qudrupole electrospray ionization mass spectroscopy (ESI-MS) in positive mode. RAC was found to be very unstable under basic condition and is converted into 2-(3-(acetylthio)-2-benzylpropanamido) acetic acid and 2-benzyl-N-(2-hydroxyvinyl) acrylamide. The drug is more stable at neutral pH as compared to acidic and oxidative stress. Under acidic conditions, benzyl 2-(2-benzyl-3-mercaptopropanamido) acetate is the probable degradation product. A stability indicating HPLC method was developed for quantitation of RAC. A strict control should be exerted on the level of basic impurities in formulations.