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青蒿素是一种常用的抗疟药,但青蒿中其他组分的药效作用很少被考察。研究发现,当青蒿中的青蒿乙素、青蒿酸、东莨菪内酯3种组分与青蒿素按照质量比为1:1:1:1的比例在小鼠体内考察药效时,与等剂量青蒿素单用组相比可以起到显著的抗疟增效作用。建立血浆中同时检测青蒿素、青蒿乙素、青蒿酸和东莨菪内酯4种组分含量的HPLC-MS方法,有助于这种增效现象在药动学层面研究的进一步开展。采用Agilent公司1200-6130液质联用系统,电喷雾电离源,正离子和负离子检测方式,SIM模式;色谱分离采用Agilent Zorbax SB-C_(18)色谱柱(2.1 mm×150 mm,5μm),流动相乙腈-0.5%乙酸水溶液(60:40),流速0.3 mL·min~(-1),柱温为40.0℃,进样量5μL。结果显示,4组分血浆浓度在5~3 000μg·L~(-1)呈现良好线性关系,方法专属性、准确度、精密度良好,无基质效应。该方法适用于小鼠血浆中青蒿素、青蒿乙素、青蒿酸和东莨菪内酯的含量测定,可用于开展4组分小鼠体内药物动力学研究。
Artemisinin is a commonly used anti-malarial drug, but the pharmacodynamic effects of the other components of Artemisia annua are seldom investigated. The study found that when artemisinin artemisinin, artemisinic acid, scopoletin three components and artemisinin in accordance with the mass ratio of 1: 1: 1: 1 ratio in mice in the study of pharmacodynamics , Compared with the same dose of artemisinin alone group can play a significant anti-malarial synergy. The establishment of simultaneous determination of four components of artemisinin, artemether, artemisinic acid and scopine lactone in plasma by HPLC-MS method is helpful for the further development of this synergism in pharmacokinetic studies . Agilent 1200-6130 liquid chromatography-mass spectrometry system, electrospray ionization source, positive and negative ion detection mode and SIM mode were adopted. The chromatographic separation was performed on an Agilent Zorbax SB-C 18 column (2.1 mm × 150 mm, 5 μm) The mobile phase was acetonitrile-0.5% acetic acid aqueous solution (60:40), the flow rate was 0.3 mL · min -1. The column temperature was 40.0 ℃ and the injection volume was 5μL. The results showed that the plasma concentration of 4 components showed a good linearity in the range of 5 ~ 3 000 μg · L -1. The specificity, accuracy and precision of the method were good and no matrix effect was found. The method is suitable for the determination of artemisinin, artemether, artemisinic acid and scopine lactone in mouse plasma, and can be used for pharmacokinetic studies in four groups of mice.