米托蒽醌的合成及质量评价

Synthesis and Quality Evaluation of Mitoxantrone

目的:合成米托蒽醌并对其进行质量评价。方法:采用1,4,5,8-四羟基蒽醌为原料,氩气保护下,50℃水浴条件中与N-(2-羟乙基)乙二胺反应2h,经干空气缓慢氧化4h后制得米托蒽醌粗品,粗品结晶以乙醇-正己烷(4∶1,V/V)混合液热溶冷却过夜析晶后,经乙醇-正己烷混合液多次洗涤制得米托蒽醌精品。考察精品(4批)的熔点、水溶液pH、紫外-可见吸收光谱、红外结构特征、干燥失重(失水率)和临界相对湿度(CRH)等,采用高效液相色谱(HPLC)法测定其中米托蒽醌的含量。结果:成功合成米托蒽醌,合成产率为34.3%,熔点为159.1~163.6℃,水溶液显碱性(pH为7.63~9.54),235~245nm波长范围内出现紫外最大吸收峰,590~600nm波长范围内出现可见光最大吸收峰,红外特征与《药品红外光谱集》(2015年版)米托蒽醌项下描述一致,失水率为-0.83%~2.36%,CRH为54.7%,HPLC法测得平均含量为78.1%(n=4)。结论:本文通过温和、无毒无害的试验条件成功合成米托蒽醌,合成步骤简单、成本低廉、产率高,合成产品质量符合相关要求。

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.