A comprehensive stability-indicating HPLC method for determination of chloroquine in active pharmaceutical ingredient and tablets: Identification of oxidation impurities.

Malaria is the most common parasitic disease in humans. It is estimated that 3 billion people live under the risk of contracting this disease in the world. Chloroquine (CQ) is the drug of choice to treat cases of non-complicated malaria. Forced degradation studies are important to know the drug's potentials degradation products and to develop a stability indicating method. Thus, chloroquine active pharmaceutical ingredient (API), chloroquine tablets and placebo were submitted to a detailed forced degradation study, using several stressing agents. The results were used on the development of a stability indicating method, using high performance liquid chromatography. The method was validated showing selectivity, precision, accuracy, robustness and linearity in the range of 30-360μg/mL of chloroquine. Chloroquine API and tablets were susceptible to alkaline hydrolysis with NaOH 1mol/L, and to oxidation with HO 3.0%. Two degradation products were formed in oxidative test. Kinetics of chloroquine degradation in alkaline hydrolysis was performed for both API and tablets. The calculated decay constant (k) was 0.223days for API and 0.182days for tablets, while the half-life (t) was 3.1days for API and 3.8days for tablets. Chemical structures have been proposed for the two degradation products formed in the presence of HO, using an UHPLC-UV-MS/MS approach.