HPLC-MS法测定犬血浆中三七皂苷R_1的血药浓度及其药代动力学

Pharmacokinetics of notoginsenoside R_1 in Beagle dogs by LC-MS

目的:建立用于测定三七皂苷R1血药浓度的液相色谱-质谱联用分析方法,并研究三七皂苷R1在犬体内的药代动力学.方法:Beagle犬6只iv0.7131 mg·kg-1三七皂苷R1后采集系列血样,利用LC-MS联用系统测定血浆药物浓度,并用3P97软件拟合求算药代动力学参数.结果:三七皂苷R1浓度在5.0～2 000μg·L-1内,线性关系良好(γ=0.9996).绝对回收率高于90%,日内、日间RSD均小于15%,符合生物样品分析要求.6只Beagle犬iv 0.7131 mg·kg-1三七皂苷R1后的血药浓度-时间曲线符合二室模型,其分布和消除相的半衰期分别为38.59 min和230.06min.曲线下面积(AUC)、中央室分布容积(V)和血浆清除率(CL)分别为67353.75 mg·min·ml-1,3.53 L·kg-1和0.1068L·kg-1·min-1.结论:建立的LC-MS联用方法专属性强,灵敏度高,可用于三七皂苷R1的体内定量分析.

AIM： To establish an analytical method for determination of notoginsenoside R1 concentration in plasma and to study its pharmacokinetic profile in dogs. METHODS： Six dogs were intravenously administration of 0.7131 mg·kg^-1 notoginsenoside R1 . Blood samples were collected at various time-points after drug administration. Analytical method based on liquid chromatography-mass spectrometry（LC-MS） was established to determine the plasma concentration of notoginsenoside R1. Pharmacokinetic evaluation was carried out using the 3P97 program. RESULTS： The calibration curves were linear over the concentration ranged from 5 to 2 000 μg·L^-1 （ γ = 0.9996）. The intra-day and inter-day precisions were generally good （ 〈 15% ） at low , medium and high concentrations. The overall recovery was more than 90%. Six dogs were intravenously administration of 0.7131 mg· kg^-1 notoginsenoside R1, and an open two compartment model best described the concentration-time profiles for notoginsenoside R1 . The half-lifes for the rapid and slow distribution phase （T1/2α and T1/2β ） were 38.59 and 230.06 min, respectively. The total area under the plasma concentration/time curve （AUC）, the volume of the central compartment （V） and plasma clearance（CL） were 67353.75 mg·min·ml^-1, 3.53 L·kg^-1 and 0.1068L· kg^- 1 . min^- 1, respectively. CONCLUSION： The analytical method is sensitive, specific, rapid and reproducible, and it is suitable for pharmacokinetic studies of notoginsenoside R1.