HPLC-MS法测定犬血浆中环维黄杨星D浓度及其药代动力学研究

Determination of Cyclovirobuxine D in Plasma by LC-MS Method and Its Phamacokinetics in Dogs

目的 :建立用于测定环维黄杨星D血药浓度的液相色谱 质谱联用分析方法 ,并探讨环维黄杨星D在犬体内的药代动力学。方法 :犬 5只ig环维黄杨星D 10mg·kg-1后采集一系列血样 ,利用HPLC MS(TOF)法 ,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 :环维黄杨星D浓度在 0 5～ 2 0 0ng·ml-1线性关系良好 (r=0 9999)。提取回收率高于 80 % ,日内、日间RSD均小于 15 % ,符合生物样品分析要求。 5只犬ig环维黄杨星D 10mg·kg-1后的血药浓度 时间曲线呈二室模型 ,其吸收相、分布相和末端消除相的半衰期 (t1/ 2Ka、t1/ 2α和t1/ 2 β)分别为 1 72 ,2 82 ,14 90h ,曲线下面积 (AUC)为 1372 5± 2 19 4ng·h·ml-1。结论 :建立的HPLC MS联用方法专属性强 ,灵敏度高 ,可用于环维黄杨星D的体内定量分析。

AIM:To establish an analytical method for determination of cyclovirobuxine D in plasma and to study its pharmacokinetic profile in dogs. METHODS:Five dogs were ig given a 10 mg·kg -1dose.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 CVB-D. Pharmacokinetic evaluation was carried out using the 3p97 program. RESULT:The calibration curves were liner over the concentration range from 0.5 ng·ml -1to 200 ng·ml -1 (r=0.9999). The intra-day and inter-day precision was generally good(<15%) at low, medium and high concentrations. The extraction recovery of CVB-D was more than 80% .Five dogs were ig given a single dose of 10 mg·kg -1of CVB-D. An open two-compartment model best described the concentration-time profile for CVB-D. The half-lives for absorption phase ,distribution phase and terminal elimination phase(t 1/2Ka、t 1/2αand t 1/2β)were 1.72, 2.82 and 14.90 h respectively. The total area under the plasma concentration time curve(AUC) was 1372.5±219.4 ng·h·ml -1. CONCLUSION: The analytical method was shown to be sensitive, specific, rapid and reproducible, and was suitable for pharmacokinetic studies of CVB-D.