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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 compare the bioavailability of 1,5-dicaffeoylquinic acid with its tetraacetyl compound in rats, and to provide a reference for the screening and structural optimization of target compounds. Methods Wistar rats were randomly divided into two groups. The mice were orally administered with equimolar amounts of 1,5-dicaffeoylquinic acid (100 mg / kg) and tetraacetyl compound (133 mg / kg) respectively. The plasma samples were extracted with ethyl acetate and separated on a Ultimate C18 column (50 mm × 2.1 mm, 5 μm) using acetonitrile-water (5 mmol / L ammonium acetate, pH 5.0) as the mobile phase and liquid chromatography tandem Two compounds were monitored simultaneously by mass spectrometry. Results The two compounds showed a good linear relationship in the range of 5 ~ 1000 ng / ml. The precision, accuracy, matrix effect, extraction recovery and other indexes all met the requirements of biological samples. Tetraacetyl was rapidly converted to 1,5-dicaffeoylquinic acid, an active metabolite in rats, and no tetraacetylation and possibly triacetylation, diacetylation and monoacetylation were detected in plasma. The relative bioavailability of oral tetraacetyl to oral 1,5-dicaffeoylquinic acid in rats was 64% based on the amount of 1,5-dicaffeoylquinic acid. Conclusion The bioavailability of tetraacetyl is lower than that of 1,5-dicaffeoylquinic acid. 1,5-Dicaffeoylquinic acid is superior to tetraacetyl when developing oral preparations.