Characterization of four new photodegradation products of hydroxychloroquine through LC-PDA, ESI-MSn and LC-MS-TOF studies.

ICH recommended forced degradation on HCQ was carried out under the conditions of hydrolysis, oxidation, dry heat and photolysis. Six degradation products (I-VI) were formed under photolytic conditions in alkaline medium. The products were characterized through +ESI-MS(n), LC-MS-TOF and LC-PDA studies. The product III was identified as N-de-ethylated HCQ which is a known impurity. It was also found to form in trace amounts under acidic and alkaline hydrolytic conditions. The products I, II, IV and V characterized as N-dehydroxyethyl-7-dechloro-7-hydroxy HCQ, dechlorinated HCQ, N-dealkylated HCQ and HCQ N-oxide, respectively were identified as new degradation products of HCQ. The product VI was not characterized due to its trace levels and insufficient mass spectral data. The most probable mechanisms of degradation of HCQ to these products were outlined and discussed.