LC-MS/MS法测定大鼠血浆中丫蕊花皂苷G的浓度及其体内药动学研究

Determination of ypsilandroside G in the rat plasma by LC-MS/MS and study on its pharmacokinetics

目的采用高效液相-串联质谱（LC-MS/MS）法测定大鼠血浆中丫蕊花皂苷G的含量,并研究其在大鼠体内的药动学特征。方法采用Phenomenex Luna C18色谱柱（150 mm×2 mm,3μm）,流动相为乙腈-水（含0.1%甲酸）,流速0.2 mL·min-1,以人参皂苷Rg3为内标;分别于大鼠尾静脉注射丫蕊花皂苷G 0.25、0.5、1 mg·kg-1,给药后于不同时间点采血,经固相萃取法处理后,采用上述LC-MS/MS法测定血药浓度;采用DAS 3.0软件、非房室模型拟合药代参数。结果 0.011.0μg·m L-1丫蕊花皂苷G与峰面积的线性关系良好,方法学考察均符合要求;大鼠静脉给药后的血浆药动学参数为：t1/2=3.447±0.898 h、MRT0-∞=4.568±1.075 h、CL=0.858±0.171 L·h-1·kg,AUC、Cmax随给药剂量的增加而等比增大,符合线性药动学特征。结论所用方法简便、灵敏,结果准确,适用于大鼠血浆中丫蕊花皂苷G的含量测定及其药动学研究。

OBJECTIVE To establish an LC-MS/MS method for the determination of ypsilandroside G in rat plasma,and to study its pharmacokinetics. METHODS The separation was performed on a reverse phase Phenomenex Luna C18 column（150 mm × 2 mm,3 μm）,with the mobile phase consisted of elution of acetonitrile-water（ contain 0. 1% formic acid） at a flow rate of 0. 2 m L·min-1.Ginsenoside Rg3 was used as internal standard. After intravenous administration at the dose of 0. 25,0. 5,1 mg·kg-1 to SD rats,the blood samples of rats were collected in the different time,and pretreated by solid phase extraction and measured by LC-MS/MS. The pharmacokinetics parameters were calculated by DAS 3. 0 pharmacokinetics program and non-compartmental model. RESULTS There was a good linearity of the calibration curves over the concentration range of 0. 01-1. 0 μg·m L-1,and the investigation of methodology all accorded with the demands. The pharmacokinetics parameters after intravenous administration were as follow：t1/2 was3. 447 ± 0. 898 h,MRT0-∞was 4. 568 ± 1. 075 h and CL was 0. 858 ± 0. 171 L·h-1·kg. The AUC and Cmaxwere increasing of equal proportion as the dose,consistent with the features of linear pharmacokinetics. CONCLUSION The method is simple,accurate and sensitive,and it is suitable for the concentration determining of ypsilandroside G in rat plasma and its pharmacokinetic study.