Identification and characterization of the absorbed components and metabolites of Gandouling tablets in rats' plasma, liver, and urine by UPLC-Q-TOF-MSE

IF 2.8 3区 医学 Q2 BIOCHEMICAL RESEARCH METHODS Journal of Chromatography B Pub Date : 2025-02-05 DOI:10.1016/j.jchromb.2025.124503
Tiantian Wang , Qing Zuo , Ting Dong , Peng Wu , Shijian Cao , Hongfei Wu , An Zhou
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Abstract

Gandouling (GDL), a famous proprietary Chinese medicine, has been utilized in China's clinics for decades to treat Wilson's disease. However, its metabolism in vivo needs to be clarified. In this study, Ultra Performance Liquid Chromatography-quadrupole time-of-flight mass spectrometry-tandem (UPLC-Q-TOF-MSE) was employed to analyze the metabolic pathways of these critical components in the rat after identifying the prototypes and metabolites of GDL in the plasma, liver, and urine of both normal and copper-loaded rats. As a result, 49 components were detected in the plasma of normally administered rats, including 29 prototype compounds and 20 metabolites; and 26 components were detected in the liver of normally administered rats, including 16 prototype compounds and 10 metabolites. 43 components were detected in the plasma of copper-laden administered rats, including 25 prototype compounds and 18 metabolites; and 23 components were detected in the liver of copper-laden administered rats, including 15 prototype compounds and 8 metabolites. A total of 73 GDL-related substances were detected in the urine of rats. The study results showed that the compositions in rats' plasma, liver, and urine were similar, mainly alkaloids and anthraquinones. The alkaloid components are mainly metabolized by phase I metabolism in vivo and the metabolic pathways are methylation, demethylation, etc. The anthraquinone components are mainly metabolized by phase II metabolism in vivo, and the metabolism modes are mainly glucuronidation and sulfation. The present study comprehensively analyses the metabolic properties of GDL and sets an essential basis for further investigations on the pharmacokinetics, in vivo bioactive components, and mechanism of action of GDL.
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用UPLC-Q-TOF-MSE法鉴定肝豆灵片在大鼠血浆、肝脏和尿液中的吸收成分和代谢产物
肝豆灵(GDL)是一种著名的中成药,在中国的诊所里用于治疗肝豆状核变性已有几十年的历史。但其在体内的代谢情况尚不清楚。在本研究中,通过超高效液相色谱-四极杆飞行时间质谱串联(UPLC-Q-TOF-MSE)鉴定了正常大鼠和铜负荷大鼠血浆、肝脏和尿液中GDL的原型和代谢物,采用超高效液相色谱-四极杆飞行时间质谱串联(UPLC-Q-TOF-MSE)分析了这些关键成分的代谢途径。结果,在正常给药的大鼠血浆中检测到49种成分,包括29种原型化合物和20种代谢物;在正常给药的大鼠肝脏中检测到26种成分,包括16种原型化合物和10种代谢物。在给铜大鼠血浆中检测到43种成分,包括25种原型化合物和18种代谢物;在给药大鼠肝脏中检测到23种成分,包括15种原型化合物和8种代谢物。在大鼠尿液中共检测到73种与gdl相关的物质。研究结果表明,大鼠血浆、肝脏和尿液中的成分相似,主要为生物碱和蒽醌类。生物碱成分在体内主要通过I期代谢进行代谢,代谢途径有甲基化、去甲基化等。蒽醌类成分在体内主要通过II期代谢进行代谢,代谢方式主要为糖醛酸化和硫酸化。本研究全面分析了GDL的代谢特性,为进一步研究GDL的药代动力学、体内活性成分和作用机制奠定了基础。
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来源期刊
Journal of Chromatography B
Journal of Chromatography B 医学-分析化学
CiteScore
5.60
自引率
3.30%
发文量
306
审稿时长
44 days
期刊介绍: The Journal of Chromatography B publishes papers on developments in separation science relevant to biology and biomedical research including both fundamental advances and applications. Analytical techniques which may be considered include the various facets of chromatography, electrophoresis and related methods, affinity and immunoaffinity-based methodologies, hyphenated and other multi-dimensional techniques, and microanalytical approaches. The journal also considers articles reporting developments in sample preparation, detection techniques including mass spectrometry, and data handling and analysis. Developments related to preparative separations for the isolation and purification of components of biological systems may be published, including chromatographic and electrophoretic methods, affinity separations, field flow fractionation and other preparative approaches. Applications to the analysis of biological systems and samples will be considered when the analytical science contains a significant element of novelty, e.g. a new approach to the separation of a compound, novel combination of analytical techniques, or significantly improved analytical performance.
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