目的建立高效液相色谱法,观察芍药苷在大鼠粪便中的降解特征及其影响因素。方法培养液中的芍药苷经适当处理后以乙腈/水为流动相(1.0mL·min^-1)通过C18反相柱进行分离,在紫外波长230nm下检测。制备芍药苷样品的水溶液(PPE)、赤芍水煎液(PR)、丹参加赤芍的水煎液(SMPR)以及冠心Ⅱ号(GXⅡ)的水煎液,分别与大鼠新鲜粪便在无氧条件下培养,不同时间采样测定。药物浓度的变化应用NONMEM软件以不同的动力学模型进行解析。结果所建高效液相色谱法可以满足本研究中芍药苷测定的要求,在浓度范围0.7875~39.38mg·L^-1区间内符合线性,日内、日间的变异均小于5%。芍药苷不同组方与大鼠粪便共同培齐后约在1h之后出现降解,降解启动时间,降解速率,以及降解的方式随着芍药苷组方的不同而有所不同。结论多数情况下肠道菌群对芍药苷的降解符合一级动力学过程,但是冠心Ⅱ号组中芍药苷的降解更接近于零级动力学过程。
OBJECTIVE To develop a HPLC method for investigating the degradation characteristics and possible covariates of paeoniflorin when being incubated with rat feces. METHODS Paeoniflorin content was measured by HPLC. The separation was performed on a C18 reverse phase column with the mobile phase consisting of CH3CN-H20 at the flow rate of 1.0 mL·min^-1. The detection wavelength was at 230 nm. Four different types of paeoniflorin solution were prepared and incubated with rat feces for different times. The degradation profiles were estimated with a nonlinear mixed effect modeling program. RESULTS The HPLC method developed was satisfactory for the investigation of paeoniflorin degradation kinetics in rat feces. The liearity was in the range of 0. 787 5 39. 38 mg·L^-1. Both intra-day and inter-day variability were less than 5%. The degradation of paeoniflorin took place about one hour after the start of incubation. The degradation time delay, the rate constant, as well as the style of degradation was influenced by the types of paeoniflorin solution. CONCLUSION The change of paeoniflorin concentration in most of the four types of solutions can be described by a First-order kinetic model, except for the group of Guanxin II where the change of paeoniflorin' s concentration is fitted with a zero-order kinetic model.