5个氨基糖苷类抗菌药降解杂质的合成

Synthesis of the Degradation Impurities of 5 Aminoglycoside Antibiotics

降解产物是氨基糖苷类抗菌药共有的一类杂质,药典对其限度均有要求。文章报道了妥布霉素、西索米星、奈替米星、卡那霉素和阿米卡星降解杂质的合成方法,通过酸水解法或衍生化氧化裂解法合成了4个一级降解杂质与1个共有的二级降解杂质,HPLC纯度均大于95%。这5个降解杂质的结构经^(1)H NMR和LC-MS确证,可作为氨基糖苷类抗菌药质量控制的杂质对照品。

Degradation products are the common impurities of some aminoglycoside antibiotics,and their residue definitions are strictly controlled in the pharmacopoeia.In this paper,the synthesis methods of degradation impurities of tobramycin,sisomicin,netilmicin,kanamycin and amikacin were investigated.Four primary degradation impurities and one common secondary degradation product were prepared by acid hydrolysis or derivative oxidation with HPLC purity of more than 95%.The structures of aforementioned five compounds were confirmed by ^(1)H NMR and LCMS,which could be used as the references for the quality control of the aminoglycoside antibiotics.