甘草查尔酮A在比格犬体内的药代动力学研究
Pharmacokinetics of licochalcone A in Beagle dogs
杨文娜 1翟亚楠 1邵寒冰 1卢伟1
作者信息
- 1. 沧州市疾病预防控制中心,河北 沧州 061000
- 折叠
摘要
目的 建立测定比格犬血浆中甘草查尔酮A含量的UPLC-MS/MS分析方法,并研究甘草查尔酮A单剂量静脉注射和灌胃给药后在比格犬体内药代动力学模式.方法 比格犬以3 mg·kg-1的剂量分别进行静脉注射和灌胃给药甘草查尔酮A,采集不同时间点的血浆样品,采用UPLC-MS/MS方法测定血浆中甘草查尔酮A的浓度,采用DAS 2.1.1版软件对血药浓度-时间曲线进行统计矩拟合,计算甘草查尔酮A的药代动力学参数.结果 血浆中甘草查尔酮A的线性回归方程为:Y=0.039X+0.1959,R2=0.9997,线性范围为2～2000 μg·L-1.静脉注射甘草查尔酮A在血浆中的半衰期t1/2为6.57 h,药时曲线下面积(AUC0～t)为1665 h·mg·L-1,平均驻留时间(MRT0～t)为5.68h,清除率(CL)为2106L·h-1·kg-1.灌胃给药甘草查尔酮A在血浆中的t1/2为8.23 h,AUC0～,为397 h·mg·L-1,MRT0～t为9.35 h,口服生物利用度为23.8％.结论 甘草查尔酮A在血浆的UPLC-MS/MS方法具有良好的专属性与灵敏度.灌胃给药甘草查尔酮A具有良好的血浆暴露量及口服生物利用度.
Abstract
Objective To develop an UPLC-MS/MS to determine the concentration of licochalcone A in the plasma of Beagle dogs and the pharmacokinetics after a single dose intravenous and oral administration of licochalcone A,respectively.Methods Beagle dogs were intravenously and orally administered licochalcone A(3 mg·kg-1).The plasma samples were collected at different time spots.UPLC-MS/MS was used to determine the concentration of licochalcone A in the plasma.The plasma concentration-time curves were fit by DAS 2.1.1 software to determine the pharmacokinetic parameters of licochalcone A.Results The linear regression of licochalcone A in the plasma was:Y=0.039X+0.1959,R2=0.9997,and the linear range was 2～2000 μg·L-1.In the intravenous administration model,the half-life(t1/2)of licochalcone A in the plasma was 6.57 h,the area under the drug-time curve(AUC0～t)was 1665 h·mg·L-1,the mean residence time(MRT0～t)was 5.68 h,and the clearance rate(CL)was 2106 L·h-1·kg 1.While in the oral administration model,the t1/2 of licochalcone A in the plasma was 8.23 h,AUC0～t was 397 h·mg·L-1,the MRT0～t was 9.35 h,and the oral bioavailability was 23.8％.Conclusion The UPLC-MS/MS method is accurate and applicable for the pharmacokinetic study of licochalcone A in the plasma of Beagle dogs.Licochalcone A shows moderate oral bioavailability.
关键词
甘草查尔酮A/药代动力学/UPLC-MS/MS/口服生物利用度Key words
licochalcone A/pharmacokinetics/UPLC-MS/MS/oral bioavailability引用本文复制引用
基金项目
沧州市科技计划自筹经费项目(222106158)
出版年
2024
NETL
NSTL
万方数据