短刺小克银汉霉AS3.153菌株对雷诺嗪的代谢转化  

Microbial transformation of ranolazine by Cunninghamella blakesleana AS 3.153

作　　者：周立华[1] 唐静雅[1] 王薇[1] 孟庆彬[1] 孙璐[1] 魏冉[2] 

机构地区：[1]沈阳药科大学药学院,辽宁沈阳110016 [2]吉林省四平卫生学校,吉林四平136000

出　　处：《沈阳药科大学学报》2015年第2期116-123,共8页Journal of Shenyang Pharmaceutical University

摘　　要：目的建立能够模拟雷诺嗪在哺乳动物体内代谢的微生物模型,并应用该模型制备代谢产物。方法采用液相色谱-质谱联用法测定雷诺嗪在4种小克银汉霉转化模型中的转化产物,选择其中转化能力最强的菌株,针对雷诺嗪3种主要代谢产物进行了培养基初始pH值、底物质量浓度、转化时间等转化条件的优化。结果短刺小克银汉霉AS 3.153对雷诺嗪的转化能力最强,将其转化为9种代谢产物,采用半制备液相色谱法制备分离得到3种主要代谢产物,确证其结构分别为羟基化雷诺嗪及雷诺嗪硫酸酯结合物。结论短刺小克银汉霉AS 3.153对雷诺嗪的转化与哺乳动物代谢结果类似,可作为模拟哺乳动物体内代谢的体外模型使用。Objective To study the microbial transformation of ranolazine,a microbial model which can be used to mimic metabolism of ranolazine in mammal was established.Methods Ranolazine and its metabolites biotransformed by four strains of Cunninghamella species were determined by high performance liquid chromatography-tandem mass spectrometry（HPLC-MS^n）,and the most suitable microorganism species was selected.The transformation conditions of initial medium pH,the substrate concentrations,and the conversion time were optimized for three main metabolites.Results Cunninghamella blakesleana AS 3.153 was selected for a preparative biotransformation and nine metabolites were biotransformed.After three main metabolites were isolated and purified,they were confirmed to be momo-hydroxy ranolazine and sulfate conjugation of ranolazine.Conclusions Cunninghamella blakesleana AS 3.153 metabolizes ranolazine in a similar way to mammals,so it can be used as an in vitro model for mammalian drug metabolism.

关 键 词：雷诺嗪 微生物转化 短刺小克银汉霉菌AS 3.153 

分 类 号：R914.1[医药卫生—药物化学] R917[医药卫生—药学]