1,5-二咖啡酰奎宁酸与其四乙酰化物相对生物利用度的研究  

The relative bioavailability of 1,5-Dicaffeoylquinic acid and its tetra-acetylate

作　　者：时美慧[1] 顾若兰[1] 甘慧[1] 李俭[1] 汤晴[1] 宋佃卫[1] 吴卓娜[1] 董俊兴[2] 孟志云[1] 

机构地区：[1]军事医学科学院野战输血研究所,北京100850 [2]军事医学科学院放射与辐射医学研究所,北京100850

出　　处：《解放军药学学报》2011年第4期286-288,343,共4页Pharmaceutical Journal of Chinese People's Liberation Army

基　　金：国家十一五重大专项:"完善和全面提升临床前药物代谢动力学技术平台;"No.2009ZX909304-004

摘　　要：目的比较1,5-二咖啡酰奎宁酸与其四乙酰化物在大鼠体内的生物利用度,为目标化合物的筛选和结构优化提供参考依据。方法 Wistar大鼠随机分两组,分别灌胃给予等摩尔数的1,5-二咖啡酰奎宁酸（100 mg/kg）和四乙酰化物（133 mg/kg）。血浆样品经乙酸乙酯萃取后,以乙腈-水（5 mmol/L乙酸铵,pH5.0）为流动相,用Ultimate C18色谱柱（50 mm×2.1 mm,5μm）分离,采用液相色谱串联质谱法同时监测两个化合物。结果两个化合物均在5~1000 ng/ml范围内呈良好线性关系,精密度、准确度、基质效应、提取回收率等各项指标都满足生物样品测定的要求。四乙酰化物在大鼠体内迅速转化成活性代谢产物1,5-二咖啡酰奎宁酸,血浆中没有检测到四乙酰化物和可能的三乙酰化、二乙酰化和单乙酰化物。以1,5-二咖啡酰奎宁酸的量计算,大鼠口服四乙酰化物与口服1,5-二咖啡酰奎宁酸的相对生物利用度为64%。结论四乙酰化物的生物利用度低于1,5-二咖啡酰奎宁酸,开发口服制剂时1,5-二咖啡酰奎宁酸优于四乙酰化物。Objective To study the relative bioavailability of 1,5-dicaffeoylquinic acid and its tetra-acetylate.Methods Wistar rats were randomly divided into 2 groups,administered ig respectively with 1,5-dicaffeoylquinic acid（100 mg/kg） and its tetra-acetylate（133 mg/kg） of an equal number of moles.Analytes were extracted from plasma samples by liquid-liquid extraction with ethyl acetate,separated on a C18 reversed phase column with 5 mmol/L ammonium acetate and acetonitrile as the mobile phase.Simultaneous determination of 1,5-dicaffeoylquinic acid and its tetra-acetylate was performed by liquid chromatography-tandem mass spectrometry.Results Linearity was good over the range of 5-1000 ng/ml for each analyte.In addition,the accuracy,precision,specificity,extraction recovery and matrix effect were satisfactory.The concentration of tetra-acetylate is below the lower limit of quantitation.1,5-dicaffeoylquinic acid was detected in the rat plasma.There was no triacetylte,diacetylte or monoacetylte.The relative bioavailability of tetra-acetylate and 1,5-dicaffeoylquinic acid was 64% according to the quantitation of 1,5-dicaffeoylquinic acid.Conclusion The bioavailability of tetra-acetylate was lower than that of 1,5-dicaffeoylquinic acid.

关 键 词：1 5-二咖啡酰奎宁酸 四乙酰化物 相对生物利用度 药代动力学 液相色谱串联质谱法 

分 类 号：R969.1[医药卫生—药理学] R965[医药卫生—药学]