Background The aim of the present work was to determine potential toxicity of degradation products of febantel generated under different stress conditions mentioned in guideline Q1A (R2) laid down by International Council for Harmonization (ICH). The stability behavior of febantel was studied by subjecting it to hydrolytic, oxidative, photolytic and thermal forced degradation conditions. Results Five degradation products (DPs) were observed which were resolved using high-performance liquid chromatography (HPLC) and characterized by LC-MS/MS using positive mode of electrospray ionization. The chromatographic separation was carried out on Hypersil® BDS C18 (150 × 4.6 mm, 5 μm) column. Optimum resolution was obtained using ammonium formate buffer (10 mM, pH 3.5) and acetonitrile programmed in gradient elution mode at 281.0 nm using photodiode array detector. Conclusion The drug was found susceptible to degradation under all the stress conditions except thermal and oxidative stress. Five major unknown degradation products DP–I, DP–II, DP–III, DP–IV, and DP–V generated under photolytic, alkali, and acidic stress condition were identified and characterized by LC-MS/MS. The drug and identified degradation products were screened for prediction of in-silico toxicity using software viz. Swiss ADME, OSIRIS Property Explorer and Pro Tox II which indicated overall no toxicological concerns. Graphical abstract