Synthesis and Quality Evaluation of Mitoxantrone / 中国药房

ABSTRACT

OBJECTIVE： To synthetize the synthesis of mitoxantrone and evaluate its quality. METHODS： Crude product of mitoxantrone was prepared by slow oxidation of 1，4，5，8-tetrahydro-anthraquinone with N-（2-hydroxyethyl） ethylenediamine in water bath at 50 ℃ for 2 h under argon protection and in dry air for 4 h. The crude product was crystallized by ethanol-n-hexane  （4 ∶ 1，V/V） mixture solution， which was cooled overnight and then washed by ethanol-n-hexane mixture for many times. The melting range， pH value of solution， ultraviolet-visible absorption spectrum， infrared structural characteristics， drying weight loss （water loss rate） and critical relative humidity （CRH） of the purified products （4 batches） were investigated. HPLC method was used to determine the contents of mitoxantrone. RESULTS： The mitoxantrone was prepared successfully， and synthetic yield of mitoxantrone was 34.3％； the melting point ranged from 159.1-163.6 ℃. The aqueous solution was alkaline （pH 7.63-9.54）； there was a maximum ultraviolet absorption peak at 235-245 nm； there was a maximum absorption peak of visible light at 590-600 nm； the infrared characteristics were consistent with those described of mitoxantrone in the 2015 edition of the Infrared Spectrum Collection of Drugs； water loss rate were －0.83％-2.36％； CRH value was 54.7％， and the average content of the product was 78.1％（n＝4） by HPLC method. CONCLUSIONS： The mitoxantrone is synthesized under mild， non-toxic and harmless experiment conditions. The synthesis step is simple， the cost is low and the yield is high. The quality of products meets the quality requirements.