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UPLC-TQ-MS/MS法测定理中汤提取物灌胃给药后正常大鼠和溃疡性结肠炎大鼠体内9种主要生物活性成分的比较药代动力学研究

Comparative pharmacokinetics of nine major bioactive components in normal and ulcerative colitis rats after oral administration of Lizhong decoction extracts by UPLC-TQ-MS/MS.

作者信息

Shen Yumeng, Cui Xiang, Jiang Shu, Qian Da-Wei, Duan Jin-Ao

机构信息

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, China.

出版信息

Biomed Chromatogr. 2019 Jul;33(7):e4521. doi: 10.1002/bmc.4521. Epub 2019 Apr 4.

Abstract

Lizhong decoction (LZD), a classic formula, has been used to treat ulcerative colitis (UC) for thousands of years in clinical practice. However, the pharmacokinetic characteristics of its major bioactive components in rats under different physiological and pathological states are not clear. Thus, in this study, a rapid and sensitive analytical method, ultra-performance liquid chromatography coupled with mass spectrometry (UPLC-MS/MS) method, was developed and applied to simultaneously determine glycyrrhizic acid, liquiritin, isoliquiritin, glycyrrhizin, isoliquiritigenin, 6-gingerol, ginsenoside Rg1, ginsenoside Rb1 and ginsenoside Re in normal and UC rats after oral administration of LZD extract. A Waters BEH C UPLC column was used for chromatographic separation, while acetonitrile and 0.1% formic acid were selected as mobile phase. The linearity of nine analytes was >0.9920. Inter- and intra-day accuracy was ≤ 11.4% and precision was from 1.1 to 12.7%. Additionally, stable and suitable extraction recoveries were also obtained. The established method was validated and found to be specific, accurate and precise for nine analytes. Furthermore, it was successfully applied to the pharmacokinetic investigation of nine major components after oral administration of LZD extracts to normal and model rats, respectively. The results showed that the pharmacokinetic parameters (C , T , AUC , AUC ) in the plasma of UC rats were significantly different from those of normal rats, which could provide a reference for the clinical application of LZD.

摘要

理中汤(LZD)是一个经典方剂,在临床实践中用于治疗溃疡性结肠炎(UC)已有数千年历史。然而,其主要生物活性成分在不同生理和病理状态下大鼠体内的药代动力学特征尚不清楚。因此,本研究建立并应用了一种快速灵敏的分析方法,即超高效液相色谱-质谱联用(UPLC-MS/MS)法,用于同时测定正常大鼠和UC大鼠口服LZD提取物后血浆中的甘草酸、甘草苷、异甘草苷、甘草甜素、异甘草素、6-姜酚、人参皂苷Rg1、人参皂苷Rb1和人参皂苷Re。采用Waters BEH C UPLC柱进行色谱分离,以乙腈和0.1%甲酸为流动相。9种分析物的线性关系>0.9920。日内和日间精密度≤11.4%,准确度为1.1%至12.7%。此外,还获得了稳定且合适的提取回收率。所建立的方法经验证,对9种分析物具有特异性、准确性和精密性。此外,该方法成功应用于分别给正常大鼠和模型大鼠口服LZD提取物后9种主要成分的药代动力学研究。结果表明,UC大鼠血浆中的药代动力学参数(C 、T 、AUC 、AUC )与正常大鼠有显著差异,可为理中汤的临床应用提供参考。

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