吸光度-波长曲线下面积和药物浓度的线性关系及其在中药药动学中的应用

Linear Relationship between Area under Absorbance-wavelength Curve and Drug Concentration and Its Application in TCM Pharmacokinetics

目的研究吸光度-波长曲线下面积和药物浓度的线性关系,用于测定组分中药的总含量,并将其应用于中药药动学研究。方法通过配制系列浓度的阿魏酸钠、盐酸川芎嗪对照品溶液,以及二者不同配比的混合溶液,在200-800 nm下进行全波长扫描,观察吸光度-波长曲线下面积和浓度的线性关系,并对阿魏酸钠、盐酸川芎嗪及其混合溶液开展尾静脉注射后大鼠体内药动学的研究。结果中药单一成分和混合成分的吸光度-波长曲线下面积和浓度均具有良好的线性关系,其中阿魏酸钠和盐酸川芎嗪浓度比2:1的线性关系为AUC=0.8289C-0.1857(r=0.9997)。大鼠体内,阿魏酸钠溶液注射后,分布和消除迅速,第2 h已消除完全;盐酸川芎嗪溶液在第2 h出现浓度低值后,第8 h出现双峰现象,说明存在肠肝循环;阿魏酸钠和盐酸川芎嗪2:1混合溶液的药时曲线基本同盐酸川芎嗪溶液趋势,但血药浓度小于后者。结论吸光度-波长曲线下面积和浓度成线性的关系可用于测定组分中药的总含量,结果可靠,重现性好,为中药药动学的研究提供了一种思路和途径,为今后中药的体内研究奠定基础。

Objective To study the linear relationship between area under the absorbance-wave- length curve and drug concentration for determining the total contents of TCM components, and applied it in the resem-eh of TCM pharmacokinetics. Methods Firstly, the solutions with a series concentrations of sodi- um ferulate and ligustrazine hydrochloride reference substance and the mixed solution of two analytes with dif- ferent ratio were prepared, then the samples received a full spectrum scan in 200 to 800 nm wavelength. The linear relationship between area under the absorbance-wavelength curve and drug concentration was observed. Rats were injected via the tail vein with sodium ferulate, ligustrazine hydrochloride and the mixed soIution re- spectively, then the pharmacokinetics were studied. Results There was an excellent linear shape between the area under the absorbance-wavelength curve of single component of TCM and concentration, and there was also an excellent linear shape between the area under the absorbauce-wavelength curve of the mixed compo- nent and concentration. When the concentration ratio of sodium ferulate and ligustrazine hydroehloride was 2： 1, the linear equation was AUC=0.8289C--0.1857 （r=0.9997）. After rats were injected with sodium ferulate, its distribution and elimination were fast, and the elimination was complete at the second hour. After rats were injected with ligustrazine hydroehloride, concentration of low level appeared at the second hour and double peaks appeared at the eighth hour, which suggested that enterohepatie circulation was existed. The curve ten- dency of the mixed solution was the same to that of ligustrazine hydrochloride, but its blood drug level was less than that of the latter. Conclusion The linear relationship between area under the absorbance-wave- length curve and drug concentration can be used to determine the total contents of TCM components. The re- suits are reliable and with a good reproducibility, which provide feasible thread and way for the research of TCM pharmacokinetics, and also lay a foundation for studying TCM in vivo.