螺内酯代谢物血药浓度的测定及健康人体药动学

RP-HPLC determination of canrenone metabolite of spironolactone and pharmacokinetics in human plasma

目的:建立反相高效液相色谱法测定螺内酯的代谢物——坎利酮的血药浓度,并研究其在健康人体的药动学。方法:以乙酸乙酯为萃取溶剂,采用 Hypersil C_(18)柱(4.6 mm×250 mm,5 μm),流动相:乙腈-0.02 mol·L^(-1)磷酸氢二铵溶液(45:55);流速为1.0 mL·min^(-1),检测波长为280 nm。结果:坎利酮在9.375～300μg·L^(-1)范围有良好色谱响应线性关系(r=0.9999),提取回收率均大于73.3%,日内与日间 RSD 均小于4.8%。人体药动学参数 C_(max)为(172.1±43.3)μg·L^(-1),T_(max)为(4.0±1.2)h,T_(1/2ke)为(16.8±4.3)h,AUC_(0-t)为(3246.1±800.4)μg·h·L^(-1),AUC_(0-∞)为(3649.1±960.4)μg·h·L^(-1)。结论:本方法是测定螺内酯活性代谢物——坎利酮血药浓度的可靠定量方法,适用于螺内酯的人体药动学研究。

Objective：To establish an HPLC method for the determination of canrenone in human plasma, which was the metabolite of spironolactone. Methods： The chromatographic column of Hypersil C18 （4.6 mm × 250 mm, 5 μm） was used. The mobile phase consisted of acetonitrile -0. 02 mol · L^-1 ammonium phosphate dibasic （45： 55） and the flow rate was 1 mL · min^-l. The detection wavelength was 280 nm. The drug was extracted from plasma with ethyl acetate. Result： The standard curve of canrenone was linear in the concentration range of 9. 375 - 300 μg · L^-1 （r =0. 9999）. Extraction recoveries were more than 73.3%. Both intra - day and inter - day RSDs were less than 4.8%. The main pharmacokinetic parameters were as follows ： Cmax （ 172. 1±43.3） μg· L^-1 Tmax（4. 0±1.2） h, T1/2ke （ 16. 8 ± 4. 3 ） h, AUC0-t（3246. 1 ± 800.4） μg · h · L^-1, AUC0-∞（ 3649.1 ∞ 960. 4 ） μg · h · L^-1, respectively. Conclusion：The HPLC method is reliable for the determination of canrenone in human plasma and suit- able for the pharmacokinetic study of spironolactone.