| 摘要: |
| [目的] 探讨干血点采样(DBS)法在热毒宁注射液药物代谢动力学试验中的应用,并与传统的血浆采集方法结果进行比较。[方法] 从志愿者肘静脉取血,一部分进行LC-MS/MS 定量分析,剩余全血分离血浆,进行栀子苷、山栀苷以及京尼平龙胆双糖苷的血药浓度分析。色谱柱Ecosil C18(150 mm×4.6 mm,5 um),流动相甲醇,20 mmol/L甲酸铵,0.1%甲酸,10%甲醇,流速0.5 mL/min,进样量10 uL。质谱检测采用ESI离子源,MRM 正离子检测模式,质谱运行采集时间11 min。[结果] 单次静脉滴注热毒宁注射液,DBS 法测定3 种栀子成分全血浓度经血细胞比容校正后,栀子苷、山栀苷、京尼平龙胆双糖苷的达峰时间(Tmax)分别为1.41、1.47、1.47 h。峰浓度(Cmax)分别为4.580、0.285、0.550 ug/mL。浓度-时间曲线下的面积(AUC0-t)分别为9.060、0.638、1.200(ug·h)/mL。平均驻留时间(Tmax)分别为1.52、1.49、1.45 h。[结论] 山栀苷、京尼平龙胆双糖苷血浆法和DBS 法(校正后)计算的血药浓度和药代参数较为一致,表明DBS 法在药物稳定性成分的药物代谢动力学研究中可替代传统血浆处理方法。 |
| 关键词: DBS法 热毒宁注射液 栀子苷 药物代谢动力学 比较研究 |
| DOI：10.11656/j.issn.1672-1519.2015.02.02 |
| 分类号: |
| 基金项目:“十二五”重大新药创制项目(2011ZX09302-006-03)。 |
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| DBS method with traditional sampling method for comparative study of human pharmacokinetics test |
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NI Tian-qing1, SI Duan-yun2, HU Si-yuan1, WEI Guang-li2, XIA Yuan-yuan2
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1.Clinical Research Institute Office, The First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China;2.State Key Laboratory of Drug Delivery Technology and Pharmacokinetics, Tianjin Institute of Pharmaceutical Research, Tianjin 300301, China
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| Abstract: |
| [Objective] Application of DBS method in Reduning injection pharmacokinetics test, and comparison of plasma collection results of traditional methods. [Methods] The elbow vein blood taken from the volunteers, some blood was quantitative analysis by LC-MS/MS quantitative analysis. We separated of the remaining blood plasma, analysis of blood drug concentration of geniposide and genipin,shanzhiside gentian diglucoside. Chromatographic column Ecosil C18 (150 mm×4.6 mm, 5 um), the mobile phase methanol, 20 mM ammonium formate, 0.1%formic acid, 10% methanol, Velocity 0.5 mL/min, sample size 10 uL. Mass spectrometric detection using ESI ion source, the MRM positive ion detection mode, acquisition time of 11 min. [Results] A single intravenous infusion of Reduning injection, the blood concentration of blood cell volume determination of three kinds of gardenia component with DBS after correction, geniposide, shanzhiside, genipin gentian diglucoside in peak time (Tmax) were 1.41, 1.47, 1.47 h. The peak concentration (Cmax) were 4.580, 0.285, 0.550 ug/mL. The area under the concentration time curve (AUC0-t) were 9.060, 0.638, 1.200(ug•h)/mL. The average dwell time (MRT0-t) were 1.52, 1.49, 1.45 h. [Conclusion] It is consistent of blood drug concentration and pharmacokinetic parameters about the shanzhiside, genipin gentian diglucoside plasma method and DBS method (after correction). It indicates that DBS method can replace the traditional plasma processing method in pharmacokinetic studies of drug stability ingredient. |
| Key words: DBS Reduning injection geniposide pharmacokinetics comparative study |
