Degradation Studies of Tadalafil: Identification, Isolation and Structure Characterization of Stress Degradation Product using LC-MS, Mass Mediated Prep-HPLC, NMR, HRMS

Abstract

The degradation behaviour of tadalafil performed under different stress conditions according to International Conference on Harmonization guidelines (ICH) was studied. A novel degradation product (DP) of tadalafil was observed only in acidic condition. An isolated degradation product [(R)-3-((1H-indol-3-yl)methyl)-4-(benzo[d][1,3]dioxole-5-carbonyl)-1-methylpiperazine-2,5-dione)] was identified by UPLC-MS technique and its structure was confirmed by high resolution mass spectrometry (HRMS) and nuclear magnetic resonance (NMR) studies. Acquity BEH C18 (50 mm × 2.1 mm, 1.7 μm) column was used in LC-MS, gradient run was performed with mobile phases 0.05% formic acid in acetonitrile and 0.05% formic acid in water, flow rate was 0.6 mL/min. The sample was diluted with acetonitrile and water.