人参皂苷Rb2在大鼠体内的药代动力学行为及代谢产物研究

建立快速高分离度液相色谱-四极杆飞行时间质谱联用方法(RRLC-Q-TOF-MS),分析人参皂苷Rb2在大鼠体内的药代动力学行为,并探索人参皂苷Rb2在大鼠体内的代谢过程.采用Agilent SB-C18色谱柱,流动相A为0.1％甲酸溶液,B为乙腈,流速为0.2 mL/min,进样量为5μL,二元线性梯度洗脱分离,采用电喷雾负离子模式进行质谱检测.方法的检出限(S/N=3)和定量限(S/N=10)分别为0.08 μg/mL和0.1 μg/mL,线性范围为0.10～ 1.26 μg/mL.结果表明,人参皂苷Rb2静脉注射后的体内代谢过程符合二室模型特征,血药浓度半衰期的α相(t1/2α)和β相(t1/2β)分别为(23.58±1.10)和(1306.55±147.23) min.通过对静脉注射人参皂苷Rb2的大鼠尿液和口服后的粪便样本进行分析,发现Rb2的代谢产物为M6,M2(C-Y),F2,C-K.

Pharmacokinetic and Metabolic Studies of Ginsenoside Rb2 in Rats

A rapid resolution liquid chromatography coupled with quadrupole-time-of-flight mass spectrometric (RRLC-Q-TOF-MS) method was established and optimized for the analysis of pharmacokinetic behavior of ginsenoside Rb2 in rats by intravenous injection administration.The metabolism of ginsenosides Rb2 in vivo rat was also explored.In the experiment,Agilent SB C18 column was selected for the sample separation with 0.1％ aqueous formic acid solution as mobile phase (A) and acetonitrile as mobile phase (B) at a flow rate of 0.2 mL/min,and the injection volume was set to 5 μL.Q-TOF-MS was carried out in electron pray ionization (ESI) negative ion mode.The limit of quantification (LOQ,S/N =10) and limit of detection (LOD,S/N=3) were 0.10 and 0.08 μg/mL,respectively,and the linear range was 0.1-1.26 μg/mL.The experiment results showed that the concentration-time profile of ginsenoside Rb2 conformed to a two-compartment pharmacokinetic model after intravenous administration for rats.The mean plasma elimination half-lives were (23.58±1.10) min (t1/2α),(1306.55±147.23) min (t1/2β) for Rb2.By analyzing the urine of rats after intravenous administration and the fecal samples after oral administration of ginsenoside Rb2,it was found that the metabolites were M6,M2 (CY),F2,and C-K.