Peroxidation of the antimalarial drug primaquine: characterization of a benzidine-like metabolite with methaemoglobin-forming activity

Abstract

1. An organic solvent-extractable product was obtained from incubations of primaquine (70mM) with H₂O₂ (70mM) and horseradish peroxidase (0.5 mg/ml) in acetate buffer, pH4.2.

2. The metabolite was characterized as 5,5-di-(8-[(4-amino-1-methylbutyl)amino]-6-methoxyquinoline by ¹H-n.m.r., mass, FT-i.r. and u.v.-visible spectroscopy.

3. Incubations of rat erythrocytes with 5,5-di-(8-[(4-amino-1-methylbutyl)amino]-6-methoxyquinoline led to the formation of methaemoglobin in a time- and metabolite concentration-dependent manner.