穿心莲内酯片在Beagle犬体内的药动学

Pharmacokinetics of Andrographolide Tablets in Beagle Dogs

本试验建立了特异性强和灵敏度高的LC-MS/MS法测定Beagle犬血浆中穿心莲内酯(1)的含量,并研究了1片口服给药后在Beagle犬体内的药动学性质。本方法以甲苯磺丁脲(2)作为内标,采用液液萃取进行犬血浆样品前处理,并进行LC-MS/MS分析。色谱采用Acquity UPLC BEH C_(18)柱,以乙腈∶2 mmol/L乙酸铵水溶液作为流动相,质谱采用电喷雾离子源负离子模式,多反应监测,监测离子对m/z 394.14→m/z 287.26(1),m/z 268.87→m/z 169.94(2)。结果显示,Beagle犬单次口服1片(15 mg/kg)后,其主要药动学参数为:t_(1/2)(3.35±3.08)h,AUC_(0→t)(375±189)ng?ml^(-1)·h,c_(max)(139.0±49.3)ng/ml。

In this study, a selective and sensitive LC-MS/MS method was developed and validated for the determination of andrographolide（1） in beagle dogs＇ plasma after oral administration of andrographolid tablets. The analytes and tolbutamide（internal standard, 2） were separated on a Waters Acquity UPLC BEH C18 column, with the mobile phase of acetonitrile and 2 mmol/L ammonium acetate solution for linear gradient elution. The mass spectrometer was operated in negative-ion and multiple reaction-monitoring（MRM） mode, with the transitions of m/z 394.14→m/z 287.26 and m/z 268.87→m/z 169.94 for 1 and 2, respectively. This method was successfully applied in the investigation of the pharmacokinetic profile of 1 in Beagle dogs after oral administration of 1 tablets. After single oral administration of 15 mg/kg to Beagle dogs, the main pharmacokinetic parameters were determined as follows： t1/2（3.35±3.08） h, AUC0→t（375±189）ng·ml-1·h, cmax（139±49.3） ng/ml.