【摘要】 目的:建立一种普适的中药复杂组分蛋白结合率的研究方法,并考察化合物极性与其蛋白结合率之间的关系。方法:在大鼠、犬和人血浆中加入低、中和高浓度3种不同浓度的五味子木脂素提取物,采用超滤法制备血浆中五味子木脂素的游离成分;然后通过LC-IT-TOF/MS分别测定血浆及超滤液中的五味子木脂素类成份的浓度;为了解决中药复杂组分定量过程中标准品严重缺乏的难题,本研究采用相对定量法,即以系列浓度的五味子提取物配制标准工作曲线,用于计算出血浆和游离态的五味子木脂素的相对浓度,并计算各木脂素的蛋白结合率;此外,以绝对定量法测定5种具有对照品的蛋白结合率,用于考察上述相对测定法的可靠性。结果:以相对定量法和绝对定量法测得的5种具有对照品的木脂素在血浆中的蛋白结合率结果一致;31种五味子木脂素与大鼠血浆、人血浆和犬血浆蛋白结合率无显著差异;随着极性的降低各木脂素的蛋白结合率增加。结论:本研究所建立的相对定量法可用于中药复杂组分的药代动力学及其蛋白结合率研究中,研究结果还发现:蛋白结合率与化合物的极性相关,化合物的蛋白结合率随着其极性的降低而升高。更多还原

【Abstract】 The main objective of the current study was to develop a universal method for a protein binding assay of complicated herbal components,and to investigate the possible relationship between compound polarity and protein binding using Schisadra lignans as an example.Firstly,the rat,dog and human plasma were spiked with three different concentrations of Schisandra chinensis extract(SLE),and ultramicrofiltration was used to obtain the unbound ingredients.Secondly,thirty-one Schisandra lignans in total plasma and ultrafiltered fluid were measured by LC-IT-TOFMS.Lastly,a relative exposure approach,which entailed calculating the relative concentrations of each Schisandra lignan from the corresponding calibration equation created from the calibration samples spiked with the stock solution of SLE,was applied in order to overcome the absence of authentic standards.The results showed that Schisandra lignans exhibited a high capability to bind with plasma protein,furthermore,the protein binding ratio of the lignan components increased proportionally with their individual chromatographic retention time,which indicated that the ratio of protein binding of lignans might increase accordingly with decreasing polarity.This study suggested that the compound polarity might be an important factor affecting the plasma protein binding of herbal components.更多还原