Przemysl Chemiczny, Vol.81, No.5, 324-327, 2002
The history of the cytostatic generic domestic drug Mitoxantrone in Poland
The 1984-1990 studies on the synthesis of 1,4-dihydroxy-5,8-bis-{2-[(2-hydroxyethyl)amino]}-9,10-anthracenedione dihydrochloride (CAS [70476-82-3]), an active substance of a Polish drug Mitoxantrone used as an antineoplastic agent, are reviewed. The Polish route starts with a crude technical-grade 5,8-dihydroxyleucoquinizarin which, after condensation with an appropriate aminoalcohol and oxidation, gives 1,4-bis-substituted aminoanthraquinone that is converted into the dihydrochloride. The highly purified (> 99%) mitoxantrone dihydrochloride preparation method is the basis of a Polish Patent 155100 (1989). Pharmacological and clinical trials of a finish formulation that was also worked up at Pharmaceutical Research Institute, were performed by using a reference drug. The Polish generic drug Mitoxantrone (20 mg/ml vials) was registered in 1990 and is manufactured by Jelfa Co. Ltd.