基于UPLC-MS/MS技术和外翻肠囊模型探究M10-H和M10-Na在肠吸收的特征

Study of the absorption characteristics of M10-H and M10-Na based on UPLC-MS/MS and everted intestinal sac model

目的:利用大鼠外翻肠囊模型,探究杨梅素衍生物杨梅素-3-O-β-D-乳糖苷(M10)在小肠的吸收特征。方法:建立M10在以台式营养液为基质的超高效液相色谱串联质谱法(UPLC-MS/MS)的定量检测方法,并进行方法学验证。本实验设置M10-H组和M10-Na组,利用大鼠外翻肠囊法体外检测M10的吸收情况,计算并比较不同肠段的各个不同时间的累计吸收量和吸收速率常数。结果:不同肠段对M10的吸收无统计学差异(P>0.05),杨梅素-3-O-β-D-乳糖苷钠盐(M10-Na)的小肠吸收量和杨梅素-3-O-β-D-乳糖苷(M10-H)相比有极显著性提升(P<0.01),M10-H的小肠段平均累积吸收量仅有M10-Na的(43±18)%。结论:在一定浓度范围内(小肠内受试化合物浓度为0.1 mg·mL^(-1)左右时)M10-H和M10-Na在小肠的不同肠段,均为线性吸收,符合零级吸收速率。

Objective:To investigate the absorption characteristics of myricetin-3-O-β-D-lactose(M10-H)and myricetin-3-O-β-D-lactose sodium salt(M10-Na)in different small intestine segments of rats by everted gut sac.Methods:UPLC-MS/MS method of M10-H and M10-Na was established and the methodology was verified.The intestinal absorption function of rats in the M10-H group and M10-Na group were detected in vitro by using the everted intestine method.The cumulative absorption and absorption rate constants of the intestine were calculated and compared.Results:There was no significant difference in the absorption rate of M10 between the duodenum,jejunum and ileum(P>0.05).The intestinal absorption of M10-Na was significantly higher than that of M10-H(P<0.01).The average cumulative absorption of M10-H was only(43±18)%that of M10-Na.Conclusion:Within a certain concentration range(when the concentration of the tested compound in the small intestine is about 0.1 mg·mL^(-1)),the absorption of the two compounds in different segments of the small intestine is linear,in accordance with the zero order absorption rate.