基于LC-MS/MS探讨楤木皂苷A在大鼠体内的药动学特性

Pharmacokinetic Study of Araloside A in Rats Based on LC-MS/MS Techniques

目的建立SD大鼠血浆中楤木皂苷A的LC-MS/MS分析方法,探讨楤木皂苷A在大鼠体内的药动学特征。方法分别灌胃、静脉注射楤木皂苷A 50和5 mg·kg^(-1)后,建立LC-MS/MS分析方法测定大鼠血浆中楤木皂苷A含量,运用DAS 3.0软件计算药动学参数。结果楤木皂苷A在1.0~10 000.0μg·L^(-1)内线性良好(r>0.994 8),专属性,精密度和准确度,基质效应和提取回收率,以及稳定性均符合要求;SD大鼠灌胃楤木皂苷A 50 mg·kg^(-1)和静脉注射楤木皂苷A 5 mg·kg^(-1),血浆中的t_(1/2)分别为(8.65±3.22)和(2.00±0.21)h,AUC_(0-t)分别为(277.14±101.00)和(21 194.59±4 385.13)ng·h·L^(-1),MRT_(0-t)分别为(7.88±0.64)和(1.21±0.11)h,Vd/F分别为(2 229.99±1 013.97)和(0.71±0.20)L·kg^(-1),CL/F分别为(149.11±62.28)和(0.24±0.05)L·h^(-1)·kg^(-1),灌胃给药ρ_(max)为(32.68±10.74)μg·L^(-1),t_(max)达到(1.21±0.70)h,楤木皂苷A的口服绝对生物利用度约为0.14%。结论本实验所建立的LC-MS/MS方法特异性强,灵敏度高,可用于楤木皂苷A的药动学研究。

OBJECTIVE To develop a highly sensitive and specific LC-MS/MS method to explore the pharmacokinetic properties of araloside A. METHODS Araloside A was administered in a dose of 50 mg·kg-1 via gastric in fusion and 5 mg·kg-1 by intravenous injection in rats.Araloside A was analyzed by a validated LC-MS/MS method in plasma after intravenous and intragastric administration. The pharmacokinetic parameters were evaluated by software DAS 3.0. RESULTS The RESULTS of pharmacokinetic study showed that the linear range of araloside A was good in 1.0-10 000.0 μg·L-1（r〉0.994 8）. The specificity, precision and accuracy, matrix effect and extraction recovery rate and stability all meet the requirements. The main pharmacokinetic parameters for intragastric administration with araloside A 50 mg·kg-1 and intravenous injection of araloside A 5 mg·kg-1 were as follows：t1/2 was（8.65±3.22） and（2.00±0.21）h, AUC0-t was（277.14±101.00） and （21 194.59±4 385.13）ng·h·L-1, MRT0-t was （7.88±0.64） and （1.21±0.11）h, Vd/F was （2 229.99±1 013.97） and （0.71±0.20）L·kg-1, CL/F was（149.11±62.28） and （0.24±0.05） L·h-1·kg-1, respectively; ρmax was （32.68±10.74） μg·L-1 for intragastric administration and tmax reached（1.21±0.70） h, oral bioavailability of araloside A was about 0.14%. CONCLUSION The LC-MS/MS method established is specific and sensitive, and can be successfully applied in basic pharmacokinetic study of araloside A in rat plasma.