LC-MS/MS法测定人血浆中伪人参皂苷GQ浓度

目的: 建立液相色谱串联质谱法测定人血浆中伪人参皂苷GQ浓度. 方法: 血浆样品中加入适量内标,以乙酸乙酯萃取后采用Waters Xevo TQS LC-MS/MS进行分析.采用Poroshell 120 EC C₈色谱柱(2.1 mm×50 mm,2.7 μm),柱温40℃,以甲醇-10 mmol·L^-1醋酸铵水溶液(80: 20)为流动相,流速0.3 mL·min^-1;采用多反应离子监测(MRM)的扫描模式,以电喷雾离子源(ESI)在负离子电离模式下进行测定. 结果: 本方法的线性范围为2.500~5 000 ng·mL^-1,最低定量限为2.500 ng·mL^-1,日内、日间精密度均小于15%,准确度在85%~115%之间,萃取回收率约9%~11%,基质效应约66%~73%,稳定性考察结果良好.药动学试验结果表明,静注伪人参皂苷GQ 120 mg·次^-1,每日1次,连续用药5 d后,达峰时间为2 h,半衰期约10 h.试验第1 d和第5 d主要药代动力学参数基本一致,计算蓄积系数分别是R_Cmax=0.964±0.099,和R_AUC=0.965±0.181,两者均接近1. 结论: 本方法适用于伪人参皂苷GQ的人体药代动力学研究.在本文给药方案下,伪人参皂苷GQ在人体内没有明显蓄积现象,连续给药不影响伪人参皂苷GQ的人体药代动力学过程.

Objective: To develop an LC-MS/MS method for the determination of pseudo-ginsenoside GQ in human plasma. Methods: The plasma samples were extracted with ethyl acetate after addition of internal standard,and then analyzed with Waters Xevo TQS LC-MS/MS system.The analytical column was Poroshell 120 EC C₈(2.1 mm×50 mm,2.7 μm)and the column temperature was set at 40℃.The mobile phase was composed of methanol-10 mmol·L^-1 ammonium acetate in water(80: 20)and the flow rate was 0.3 mL·min^-1.Detection was performed with multiple reactions monitoring(MRM)using negative electrospray ionization(ESI). Results: The calibration curve was linear over the concentration range of 2.500-5 000 ng·mL^-1.The lower limit of quantification was 2.500 ng·mL^-1.Inter-and intra-day precisions were less than 15% and accuracy was within 85%-115%.Extraction recoveries were around 9%-11% and matrix effects were around 66%-73%.The analytes were proved to be stable.The pharmacokinetic results manifested that after the intravenous infusion of pseudo-ginsenoside GQ of 120 mg qd.for consecutive 5 days,the t_max was 2 h and the t_1/2 was about 10 h.The main pharmacokinetic parameters were basically the same between day 1 and day 5.The accumulation coefficient for R_Cmax was 0.964±0.099 and that for R_AUC was 0.965±0.181,both of which were close to 1. Conclusion: This method is applicable to the pharmacokinetic study of pseudo-ginsenoside GQ in humans.With the dosage regimen in this paper,no obvious accumulation was observed and no significant changes were seen in human pharmacokinetics after multiple administrations of pseudo-ginsenoside GQ.

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