Novel stability-indicating HPLC methods have been presented for the analysis of Tasimelteon (TSM) besides its main degradation products in bulk and pseudo tablet formulations in this study. For the LC-DAD method; quantitation of TSM and its separation with other degradation products were achieved on an Ascentis Express (TM) pentafluorophenylpropyl (F-5)-bonded fused-core silica particle column (2.7 mu m particle size 100 x 4.6 mm, Supelco) using the mobile phase consisted of acetonitrile: acetate buffer (0.025 M, pH 4.5): water (40:10:50, v/v/v); the elution was performed at 0.8 mL min(-1) flow rate, detecting the compounds at 281 nm. In addition to regular in- house validation studies, the developed method was tested on another UPLC instrument to assess its ruggedness for possible method transfer demands. For the LCMS/MS method, analyte quantitation was achieved on a second-generation monolithic silica column (Chromolith(TM) High-Resolution RP-18e, 100 x 4.6 mm from Merck KGaA, Germany); the mobile phase was a mixture with 0.1 % (v/v) formic acid in water and 0.1 % (v/v) formic acid in acetonitrile (60: 40 (v/v), pH = 2.5). The instrumental and analytical performances of all three instrumental systems were compared with each other in terms of the working range, LOD, and LOQ. In addition to the above, a new degradation product was identified using LCMS-IT-TOF system. It can be concluded that among the similar ones in the literature, this study is the most comprehensive method optimization and validation study to date about TSM, in which a novel degradation product was also reported. (C) 2020 Elsevier B.V. All rights reserved.