IDENTIFICATION AND CHARACTERIZATION OF DEGRADATION PRODUCTS OF RALTEGRAVIR USING LC, LC–MS/TOF, AND MSN

Abstract

The aim of the present investigation was to carry out stress degradation studies on raltegravir according with International Conference on Harmonization (ICH) Q1A(R2) guideline. The drug was subjected to hydrolytic (acid, alkaline, and neutral), oxidative, thermal, and photolytic stress. Raltegavir showed a labile behavior in acidic, basic, and neutral stress while it was stable in oxidative, photolytic, and thermal stress conditions. In total, five degradation products (DP) were formed, which were separated on a C-18 column employing a gradient HPLC method. To elucidate the structure of degradation products, initially a complete mass fragmentation pathway of the drug was established with the help of multi-stage mass spectrometry (MSn) and mass spectrometry/time of flight (MS/TOF) accurate mass studies. Then, stressed samples were subjected to LC–MS/TOF studies, which provided their fragmentation pattern and accurate masses. The mass spectral data were employed to characterize the DPs and assign structures to them. The total information was also used to establish the degradation pathway of the drug.