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

Abstract

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 (DP-1 to DP-7) were found under diverse conditions, which were not reported earlier. The chemical structures of these degradation products were characterized by 1H NMR, 13C NMR, 2D NMR, Q-TOF-MSn and IR spectral analysis and the proposed degradation products structures were further confirmed by the individual synthesis.

New approaches to identification and characterization of tioconazole in raw material and in pharmaceutical dosage forms

“…These techniques are non-destructive, allow the analysis of liquid, solid, and semi-solid samples, allow the direct measurement of untreated samples, and do not produce hazardous wastes [9]. On the other hand, nuclear magnetic resonance (NMR) spectroscopy has evolved into an irreplaceable approach for pharmaceutical quality assessment, currently playing a critical role in unequivocal structure identification as well as in structural confirmation (qualitative detection), which enables the understanding of the underlying mechanisms of the formation of process and/or degradation impurities [10]. NMR can provide qualitative information, without the need for standards of the unknown compounds [11].…”