6,7-二甲氧基香豆素在大鼠体内主要代谢产物的研究

Study on Main Metabolites of 6,7- dimethoxycoumarin in Rat's Body

目的:研究大鼠单剂量ig5mg/kg6,7-二甲氧基香豆素后各生物样品中主要代谢产物。方法:采用高效液相色谱法对代谢物进行分析和分离,并利用电喷雾离子阱质谱注射泵直接进样技术及液相色谱-质谱联用技术(LC/MSn)对大鼠尿液、胆汁中6,7-二甲氧基香豆素主要代谢产物进行结构鉴定。结果:大鼠给药后0～10h内,仅在血样中检测到母体药物6,7-二甲氧基香豆素,而在尿样、粪样及胆汁中均未检出。比较服药前后的生物样品色谱行为可见,大鼠口服6,7-二甲氧基香豆素后,在胆汁中存在两个主要代谢产物(M1和M2),在血样和尿样中则以M1为主,而在粪样中未检出。由其色谱峰面积估计,代谢物M1和M2的含量占生物样品中代谢物总量的80%以上。结论:根据代谢物的色谱行为及质谱断裂规律,推定6,7-二甲氧基香豆素在大鼠体内的两个主要代谢产物(M1和M2)为6,7-二甲氧基香豆素经水解脱甲基生成的羟基化合物,均以硫酸酯结合物形式存在,且互为同分异构体。

Objective: To study the principal metabolites of all biological samples taken after having a single dose of 6,7-dimethoxycourin, 5mg/kg, by a rat orally. Method: To analyse and separate the metabolites by high performance liquid Chromatography and do structural identification of the principal metabolites of 6,7-dimethoxycourin in the bile and urine of the rat by the techniques of electro-atomizing ion-trap mass spectrometric injection pump and LC/ MSn. Result: 6,7-dimethoxycourin of the parent drug is found out by test only in the blood sample of the rat after 0-10 hours of administration while it does not emerge either in samples of urine and excrements or in bile. In comparison with the chromatographic behaviors of the biolagieal samples taken before and after the administration respectively it can be seen that two principal metabolites (M1 and M2) have been found in the bile of the rat, mainly M1 in the samples of blood and urine, instead of in the sample of excrements when the rat takes 6,7-dimethoxycourin orally. In accordance with the area of the chromatographic pick it is estimated that the contents of M1 and M2 may account for more than 80% of the total content of the metabolites in the biological samples. Conclusion: One can deduce on the basis of the chromatographic behaviors and the break regularity of the metabolites that the two principal metabolites (M1 and M2) of 6,7-dimethoxycourin in the body of the rat are of hydroxyl compound produced by demethylating 6,7 dimethoxycourin via bydrolyzation, both of which exist in the form of sulphuric solders and are isomers one another.