Simultaneous Determination and Pharmacokinetic Characterization of Glycyrrhizin, Isoliquiritigenin, Liquiritigenin, and Liquiritin in Rat Plasma Following Oral Administration of Glycyrrhizae Radix Extract
Simultaneous Determination and Pharmacokinetic Characterization of Glycyrrhizin, Isoliquiritigenin, Liquiritigenin, and Liquiritin in Rat Plasma Following Oral Administration of Glycyrrhizae Radix Extract
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DOI：
10.3390/molecules24091816
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发表时间：
2019-05-01
期刊：
影响因子：
4.6
通讯作者：
Song, Im-Sook
中科院分区：
文献类型：
--
作者：
Han, You Jin;Kang, Bitna;Song, Im-Sook
甘草被广泛用作草药，对炎症、各种癌症和消化系统疾病有效。建立了一种灵敏的同时测定大鼠血浆中甘草酸苷、异甘草素、甘草素和甘草苷的高效液相色谱-串联质谱法，并将其应用于药代动力学研究。甘草酸、异甘草素、甘草素和甘草苷的保留时间分别为7.8min、4.1min、3.1min和2.0min，说明四种分析物在峰洗脱时间附近分离良好，没有干扰峰。甘草酸和异甘草素、甘草素、甘草苷的定量下限分别为2 ng/m L和0.2 ng/m L，日内和日间精密度、稳定性均小于15%。4只大鼠单次口服1g/kg GRE后，24小时内测定血浆中甘草酸、异甘草素、甘草素和甘草苷的浓度。甘草甜素血药浓度最高，半衰期较长(23.1+/-15.5h)。有趣的是，在GRE给药后4-10h，异甘草素和甘草素的血浆浓度恢复到初始浓度，这表明在粪便裂解物和肠壁酶的催化下，甘草素生物转化为异甘草素和甘草素。总之，我们建立的检测甘草酸、异甘草素、甘草素和甘草苷的分析方法可以成功地用于研究它们在大鼠体内的药代动力学特性，并将有助于进一步研究GREs及其标志物成分的疗效、毒性和生物药剂学。
Glycyrrhizae Radix is widely used as herbal medicine and is effective against inflammation, various cancers, and digestive disorders. We aimed to develop a sensitive and simultaneous analytical method for detecting glycyrrhizin, isoliquiritigenin, liquiritigenin, and liquiritin, the four marker components of Glycyrrhizae Radix extract (GRE), in rat plasma using liquid chromatography-tandem mass spectrometry and to apply this analytical method to pharmacokinetic studies. Retention times for glycyrrhizin, isoliquiritigenin, liquiritigenin, and liquiritin were 7.8 min, 4.1 min, 3.1 min, and 2.0 min, respectively, suggesting that the four analytes were well separated without any interfering peaks around the peak elution time. The lower limit of quantitation was 2 ng/mL for glycyrrhizin and 0.2 ng/mL for isoliquiritigenin, liquiritigenin, and liquiritin; the inter- and intra-day accuracy, precision, and stability were less than 15%. Plasma concentrations of glycyrrhizin, isoliquiritigenin, liquiritigenin, and liquiritin were quantified for 24 h after a single oral administration of 1 g/kg GRE to four rats. Among the four components, plasma concentration of glycyrrhizin was the highest and exhibited a long half-life (23.1 +/- 15.5 h). Interestingly, plasma concentrations of isoliquiritigenin and liquiritigenin were restored to the initial concentration at 4-10 h after the GRE administration, as evidenced by liquiritin biotransformation into isoliquiritigenin and liquiritigenin, catalyzed by fecal lysate and gut wall enzymes. In conclusion, our analytical method developed for detecting glycyrrhizin, isoliquiritigenin, liquiritigenin, and liquiritin could be successfully applied to investigate their pharmacokinetic properties in rats and would be useful for conducting further studies on the efficacy, toxicity, and biopharmaceutics of GREs and their marker components.