光谱法测定大鼠血浆中茯苓多糖硫酸酯及其药代动力学研究

目的:利用光谱探针天青A(AA)与硫酸化多糖之间产生变色反应的特性建立大鼠血浆中茯苓多糖硫酸酯(PS)的光谱测定方法,测定大鼠腹腔注射和尾静脉注射PS后的血药浓度,并对这2种注射方法的药代动力学进行评价。方法:通过扫描和系列实验确定最佳检测波长、反应体系血浆和AA浓度。大鼠腹腔和尾静脉分别注射60,20 mg.kg-1的PS后,测定血浆中不同时间点的PS质量浓度,并计算主要药动学参数。结果:最佳检测波长为620 nm,反应体系血浆加入量最大为1.25%,AA最佳工作浓度为8.24×10-5mol.L-1,血浆中PS质量浓度在0~10 mg.L-1线性关系良好(R2=0.995 9),平均回收率为100.55%,组内和组间差异RSD均小于5%。大鼠腹腔和尾静脉注射PS的消除相半衰期t1/2(ke)分别是319.09,204.85 min,血液PS的消除符合一房室、一级消除的开放模型,腹腔注射给药的生物利用度F为69.12%。结论:本光谱法灵敏度高,操作简便,重复性和稳定性好,尤其适合于药代动力学的分析研究。

Determination of plasma concentration of pachyman sulfate by spectrophotometry and its pharmacokinetics after intraperitoneal and intravenous administrations in rats

Objective: To develop a spectral assay for determination of pachyman sulfate (PS) in rat plasma and to study the pharmacokinetics after intraperitoneal and intravenous administrations of PS. Method: The spectral probe azur A (AA) was used to measure the concentration of PS in rat plasma, since AA could combine the sulfate groups in PS molecules and consequently induced the color change in solution. The optimal wavelengths, concentrations of plasma and AA in reaction system were determined by spectral scanning and serial tests. The plasma PS concentrations were measured at different time after intraperitoneal and intravenous administrations at the dosage of 60 and 20 mg·kg^-1, respectively. Result: The optimal detecting wavelength was 620 nm. The maximum concentration of plasma and the optimal concentration of AA were 1.25% and 8.24×10^-5 mol·L^-1 in reaction system, respectively. The calibration curve was linear over the range of 0-10 mg·L^-1 with a correlation coefficiency of 0.995 9. The mean recovery was 100.55%. The relative standard deviation (RSD) of intra-group and inter-group were all less than 5%. After intraperitoneal and intravenous administrations, the corresponding elimination half-lives were 319.09 min and 204.85 min, respectively. The elimination of PS in blood matched the open model of one compartment and first-order elimination. The bioavailability of PS via intraperitoneal injection was 69.12%. Conclusion: The spectral probe AA was convenience, sensitive, accurate and steady to use for measuring the concentration of PS in the blood of rats; this made the research work of PS-pharmacokinetics easy and concise.