Novel degradation products of argatroban: Isolation, synthesis and extensive characterization using NMR and LC-PDA-MS/Q-TOF.

Forced degradation study of argatroban under conditions of hydrolysis (neutral, acidic and alkaline), oxidation, photolysis and thermal stress, as suggested in the ICH Q1A (R2), was accomplished. The drug showed significant degradation under hydrolysis (acidic, alkaline) and oxidation (peroxide stress) conditions. The drug remained stable under thermal and photolytic stress conditions. In total, seven novel degradation products (DP1 to DP7) were found under diverse conditions, which were not reported earlier. The chemical structures of these degradation products were characterized by H NMR, C NMR, 2D NMR, Q-TOF-MS and IR spectral analysis and the proposed degradation products structures were further confirmed by the individual synthesis.