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小白菊内酯是小白菊(Tanacetum parthenium)中的主要活性成分,具有抗炎和抗癌的药理活性。本研究首先建立了一种专属、灵敏、准确的大鼠血浆中小白菊内酯浓度定量的LC-MS/MS检测方法,采用一步液-液萃取法从大鼠血浆中提取待测物及内标,以水-甲醇为流动相系统对待测物进行分离。标准曲线范围为2~128ng·mL~(-1),精密度、准确度均符合要求,并且提取回收率较高。利用此检测方法对体外放置大鼠血浆样品中小白菊内酯的稳定性进行了考察,结果显示高、中、低3个浓度的小白菊内酯在30 min后均有超过15%的分解,表明其在大鼠血浆中稳定性较差。体内药动学实验分别静脉给予大鼠20、40及80mg·kg~(-1)的小白菊内酯,药动学参数显示其在大鼠体内消除较快,半衰期小于90min。高剂量80mg·kg~(-1)给药组初始浓度也仅为138.86±21.07ng·mL~(-1),并且药时曲线下面积与给药剂量非等比例增加。本研究结果为进一步开发小白菊内酯成为抗肿瘤药物提供了重要的药动学信息。
Parthenolide is the major active ingredient in Tanacetum parthenium and has anti-inflammatory and anticancer pharmacological activity. In this study, we established a specific, sensitive and accurate LC-MS / MS method for the determination of the concentration of parthenolide in rat plasma. One-step liquid-liquid extraction was used to extract the analytes from the plasma of rats , With water - methanol as the mobile phase system to be tested for separation. The standard curve ranged from 2 to 128 ng · mL -1. The precision and accuracy of the standard curve met the requirements and the extraction recovery rate was high. The stability of parthenolide in rat plasma samples was investigated by this method. The results showed that the high, medium and low concentrations of Parthenolide had more than 15% decomposition after 30 min, Its stability in rat plasma is poor. In vivo pharmacokinetics experiments were given intravenous administration of 20, 40 and 80 mg · kg -1 of parthenolide respectively. The pharmacokinetic parameters showed that it was rapidly eliminated in rats and the half-life was less than 90 min. The initial concentration of high-dose 80mg · kg -1 group was only 138.86 ± 21.07ng · mL -1, and the area under the curve of the drug dose was not proportional to the dose. The results of this study provide important pharmacokinetic information for the further development of parthenolide as antitumor drug.