Amodiaquine (AMD) is an antimalarial drug used in the treatment of malaria disease. In the present study, the drug was subjected to stress studies as per International Conference on Harmonization guidelines (ICH) Q1A (R2) to understand the drug degradation profile under different stress conditions. It was observed that the drug degraded under base hydrolytic conditions and examined this degradation product. The DP1 was enriched and isolated by preparative HPLC and characterized by ultra-high-performance liquid chromatography coupled with time-of-flight tandem mass spectrometry (UHPLC-QTOF-MS/MS). The DP1 structure was further confirmed by nuclear magnetic resonance (NMR) experiments (1D & 2D NMR). The HPLC method was validated as per the ICH Q2 (R1) guidelines and found that the method is simple, rapid, linear, precise, and accurate. The validated method can be utilized, in the impurities identification of the bulk drug (API) or finished dosage form of amodiaquine.

Key words: Amodiaquine, Degradation product, Isolation and characterization. Structural elucidation by using LC-QTOF-MS/MS and NMR.

Abbreviations: Amodiaquine (AMD), Degradation Product (DP), Liquid chromatography time of flight mass spectrometry (LC-QTOF-MS), Nuclear Magnetic Resonance (NMR).