LC-MS/MS法测定石斛碱在大鼠体内药代动力学研究

Pharmacokinetics of Dendrobin in Rats by LC-MS/MS

目的:建立LC-MS/MS分析方法测定大鼠血浆中石斛碱浓度,考察其体内药代动力学特征。方法:SD大鼠6只灌胃给予石斛碱(20 mg/kg),于给药前及给药后5、15、30、45、60、90.120、180、240、420、600、1 440 min眼内眦静脉从取血,测定大鼠血浆石斛碱浓度。用DAS2.0统计软件计算药动学参数。结果:石斛碱浓度在0.5~50 ng/m L范围内线性关系良好(r2=0.999 2),定量下限为0.5 ng/m L,低(1 ng/m L)、中(5 ng/m L)、高(20 ng/m L)3个浓度的回收率分别为(78.86±4.56)%、(85.25±1.23)%及(80.56±2.23)%;日内及日间RSD均小于10%。石斛碱给药后血药浓度-时间曲线符合二室模型,消除半衰期为t1/2为(51.27±2.65)min,Tmax为(10.00±0.17)min,Cmax为(0.12±0.08)mg/L,AUC(0-∞)为(7.91±0.25)mg/L·min。结论:本分析方法对石斛碱体内外检测具有专属性,且灵敏、可靠,适用于石斛碱药代动力学研究。

Objective: To establish an LC-MS/MS method for determination of dendrobine,and to study the pharmacokinetics of dendrobine in rats. Methods: Six male rats were orally administered with Dendrobium(20 mg/kg),Plasma samples were collected at 5、15、30、45、60、90.120、180、240、420、600、1440 min after the drug administration.The pharmacokinetic parameters were calculated by DAS2.0 software. Results: The calibration curves were linear over the concentration ranging from 0.5 to 50 ng/mL(r2=0.9992)with the LLOQ of 0.5 ng/mL.The intraday and interday RSD were generally good(<10%).The concentration-time curve for dendrobine was in accordance with the two-compartment model,The main pharmacokinetic parameters t 1/2 ,T max ,C max ,AUC (0-∞) were as follows:(51.27±2.65)min,(10.00±0.17)min,(0.12±0.08)mg/L,(7.91±0.25)mg/L·min. Conclusion: The analytical method developed is sensitive specific rapid and reproducible and is proved to be suitable for the pharmacokinetic study of dendrobine.