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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 establish a microbiological model that simulates the metabolism of ranolazine in mammals and to use this model to prepare metabolites. Methods Liquid chromatography-mass spectrometry (GC-MS) was used to determine the conversion products of ranolazine in four strains of C. ginkgo, and the strains with the highest transformation ability were selected. The primary metabolites of ranolazine , Substrate concentration, transformation time and other transformation conditions optimization. The results showed that Acinetobacter baumannii AS 3.153 had the strongest transformation ability to ranolazine, which was transformed into nine metabolites. The three major metabolites were isolated and purified by semi-preparative liquid chromatography, and the structures were confirmed to be hydroxylated Ranolazine and ranolazine sulfate conjugate. CONCLUSIONS The transformation of ranolazine to S. gindii AS 3.153 was similar to that of mammals and could be used as an in vitro model to mimic mammalian in vivo metabolism.