Forced Degradation studies of CNS Drugs and Identification of Possible Degradants by Chromatographic Techniques

Abstract

Forced degradation studies under rigorous conditions should be conceded on drug to find out the inherent strength character also degradation pathway to maintain the correctness of the planned analytical procedures. Further, the identification of degradants in pharmaceuticals is critically important for reasons of both product efficacy and patient safety. There are no reports for the identification of degradants by chromatographic techniques for the recent CNS drugs viz Ezogabine and Zolpidem tartrate. Complete LC plus LCMS method of degradation behavior on these CNS drugs under different ICH prescribed stress conditions have also be deficient. Ezogabine or retigabine (RTG) chemically called as N-(2-amino-4-(4-fluorobenzylamino) phenyl) carbamic acid ethyl ester. The drug is a new anti-epileptic drug and the drug is not official in IP, BP and USP. The drug is a colorless and freely soluble in polar solvents. Zolpidem tartrate (ZOL), chemically called as N, N-dimethyl-2-[6-methyl-2-(4-methylphenyl) imidazo [1, 2-a] pyridin-3-yl] acetamide L (+) tartrate. The drug is used as hypnotic. The drug is a colorless crystalline powder and sparingly soluble in alcohol plus water. Zolpidem tartrate is official in IP20 (2014) and USP20 (2011). IMPACT OF THE STUDY: Developed and validated a stability indicating RP-HPLC method for the determination of selected CNS drugs like Ezogabine in bulk form and Zolpidem tartrate present in tablet dosage form. To assess stability profile of these drug /drug products during manufacturing, processing, storage conditions and safety. Forced degradation studies were carried out for the selected CNS drugs like Ezogabine and Zolpidem tartrate. Degradation product of ezogabine and zolpidem tartrate were separated by preparative HPLC method and identified by IR, NMR and mass spectral data. Degradation product of ezogabine and zolpidem tartrate were used for the determination of mutagenicity and found non mutagenic by Ames test. Full mass accountability of the degradation products was obtained.