液相色谱-电喷雾串联质谱法测定大鼠体内神化复方制剂的代谢物谱及四种生物活性化合物的药代动力学研究

IF 3.1 3区 医学 Q2 CHEMISTRY, ANALYTICAL
Ze-Xuan Chen, Ling Li, Jie Tang, Meng-Ge Shi, Xue-Yee Lim, Pei-Rong Song, Lu Zou, Han Han, Yun Gu, Tong Zhang
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引用次数: 0

摘要

由人参、山楂和槐花组成的神华复方具有改善高脂血症的作用。然而,其主要成分、体内代谢途径和药代动力学特征等尚不清楚。本研究采用超高效液相色谱-电喷雾四重飞行时间质谱法(UHPLC-Q-TOF)对神花复方乙醇提取物中的主要成分进行了定性分析,并对大鼠口服后血清、胆汁、粪便和尿液中的代谢物进行了研究。采用三重四极杆液相色谱-电喷雾质谱法(QQQ-LC/MS)分析了人参皂苷Rg1、人参皂苷Re、人参皂苷Ro和芦丁在大鼠体内的药代动力学。结果表明,神华复方中含有 48 种化合物,包括皂苷、黄酮类和有机酸。对神华复方口服后的代谢物进行了全面分析,鉴定或表征了 24 种原型成分和 92 种代谢物成分。通过分析不同剂量神化复方口服后0~72 h人参皂苷Rg1、人参皂苷Re、人参皂苷Ro和芦丁的药代动力学参数,发现人参皂苷的血药浓度保持在2 ng∙mL1以下,但代谢排泄时间延长。同时,芦丁的血药浓度明显高于人参皂苷,并出现双吸收峰。总之,本研究对神华复方口服后复方成分的体内代谢规律和药代动力学提供了有价值的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Metabolite profiling of Shenhua compound in rats and pharmacokinetics study of four bioactive compounds with liquid chromatography combined with electrospray ionization tandem mass spectrometry.

Shenhua compound, composed of ginseng, hawthorn and sophora flower, has been shown to improve hyperlipidemia. However, the main ingredients, their metabolic pathways in vivo, and pharmacokinetic characteristics. In this study, ultra-high-performance liquid chromatography coupled with electrospray ionization quadruple time-of-flight mass spectrometry (UHPLC-Q-TOF) was used to qualitatively analyze the main ingredients in ethanol extract of Shenhua compound and to investigate the metabolites in serum, bile, feces, and urine of rats following oral administration. The pharmacokinetics of ginsenoside Rg1, ginsenoside Re, ginsenoside Ro and rutin in rats were analyzed using triple-quadrupole liquid chromatography combined with electrospray ionization mass spectrometry (QQQ-LC/MS). The results indicated that 48 compounds were present in Shenhua compound, including saponins, flavonoids and organic acids. Metabolites were comprehensively analyzed after oral administration of Shenhua compound, and 24 prototype ingredients and 92 metabolite ingredients were identified or characterized. By analyzing the pharmacokinetic parameters of ginsenoside Rg1, ginsenoside Re, ginsenoside Ro and rutin from 0 to 72 h after oral administration of various dose of Shenhua compound, it was observed that the concentration of ginsenosides in blood remained below 2 ng∙mL1, but the metabolic excretion time was prolonged. Meanwhile, the blood concentration of rutin was significantly higher than ginsenosides and showed a double absorption peak. In conclusion, this study provides valuable insights into compound ingredients metabolism regularities in vivo and pharmacokinetics after oral administration of Shenhua compound.

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来源期刊
CiteScore
6.70
自引率
5.90%
发文量
588
审稿时长
37 days
期刊介绍: This journal is an international medium directed towards the needs of academic, clinical, government and industrial analysis by publishing original research reports and critical reviews on pharmaceutical and biomedical analysis. It covers the interdisciplinary aspects of analysis in the pharmaceutical, biomedical and clinical sciences, including developments in analytical methodology, instrumentation, computation and interpretation. Submissions on novel applications focusing on drug purity and stability studies, pharmacokinetics, therapeutic monitoring, metabolic profiling; drug-related aspects of analytical biochemistry and forensic toxicology; quality assurance in the pharmaceutical industry are also welcome. Studies from areas of well established and poorly selective methods, such as UV-VIS spectrophotometry (including derivative and multi-wavelength measurements), basic electroanalytical (potentiometric, polarographic and voltammetric) methods, fluorimetry, flow-injection analysis, etc. are accepted for publication in exceptional cases only, if a unique and substantial advantage over presently known systems is demonstrated. The same applies to the assay of simple drug formulations by any kind of methods and the determination of drugs in biological samples based merely on spiked samples. Drug purity/stability studies should contain information on the structure elucidation of the impurities/degradants.
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