目的建立华蟾毒配基在大鼠体内的血药浓度的HPLC测定方法,并根据血药浓度-时间数据计算其体内药动学参数。方法经舌下静脉分别注射0.251、0.503、1.006mg/kg华蟾毒配基,采用RP-HPLC法测定血清中药物浓度,用3P87药动学软件计算药动学参数。结果华蟾毒配基在大鼠体内的动力学过程可用一级动力学过程的二室开放型模型来描述。高、中、低3个不同剂量组的主要药动学参数分别为t1/2α0.4830、0.3777、0.2723h;t1/2β4.4189、5.8972、2.4682h;V(c)2.5120、8.6606、27.9378L/kg;AUC12.1970、8.4123、2.9056μg/(h·mL);CL2.0497、5.9437、34.4166L/(kg.h)。结论本研究建立的RP-HPLC测定大鼠静脉注射不同剂量华蟾毒配基后血药浓度的实验方法简便、快速、灵敏,血清中内源性物质不干扰测定,可为华蟾毒配基临床安全合理用药和制剂质量控制提供依据。

Objective To develop a RP-HPLC method for determination of cinobufagin in rat serum and to calculate the pharmacokinetic parameters of cinobufagin through blood concentration-time curve. Methods The pharmacokinetics of cinobufagin was investigated in rats after sublingual iv administration of cinobufagin in 0.251, 0.503, and 1.006 mg/kg. Serum concentrations of cinobufagin were determined by HPLC. 3P87 Pharmacokinetic program was used to describe the compartment-mode of the blood concentration-time curve of cinobufagin and to calculate the main phamacokinetic parameters. Results The blood concentration-time curves of cinobufagin following single iv administration in rats in vivo conformed to two compartment open model in one grade pharmacokinectics. The major pharmacokinetic parameters of cinobufagin (1, 0.5, and 0.25 mg/kg) were t1/2α∶ 0.483 0, 0.377 7, 0.272 3 h; t1/2β∶ 4.418 9, 5.897 2, 2.468 2 h; V(c)∶ 2.512 0, 8.660 6, 27.937 8 L/kg; AUC: 12.197 0, 8.412 3, 2.905 6 μg/(h·mL); CL: 2.049 7, 5.943 7, 34.416 6 L/(kg·h). Conclusion RP-HPLC Method is simple, rapid, sensitive, and accurate for determination of cinobufagin without any interference by endogenous substances in rat serum, which can be provided with academic foundation for clinical application and quality control of cinobufagin