Screening and identification of multiple constituents and their metabolites of Zhi-zi-chi decoction in rat urine and bile by ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry
Screening and identification of multiple constituents and their metabolites of Zhi-zi-chi decoction in rat urine and bile by ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry
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DOI：
10.1002/bmc.3978
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发表时间：
2017-10-01
影响因子：
1.8
通讯作者：
Niu, Liying
中科院分区：
文献类型：
--
作者：
Feng, Wei;Dong, Qiuju;Niu, Liying
芝子池汤是我国临床广泛应用的经典方剂。在本研究中，建立了一种新的、高效的方法来筛选和鉴定ZZCD的多种成分及其代谢物，并将其与三重飞行时间质谱仪相结合。结合多种数据处理技术，提出了一种基于多质量缺陷滤波法和动态背景减除法的在线数据采集方法。首先，在ZZCD中共检测到109种潜在的生物活性物质。在相同的仪器条件下，经口给药后的大鼠体液中共检出100种化合物，包括61种原化合物和39种代谢物。ZZCD的主要代谢反应是与硫酸盐、葡萄糖醛酸和氨基酸的结合。由于在尿液中检测到的异物比在胆汁中检测到的更多，这表明ZZCD的多种成分已经经历了全面的肾脏排泄。本研究首次报道了大鼠口服珍珠汤后的尿液和胆汁排泄情况。本研究扩大了人们对珍珠汤化学成分和代谢的认识，对进一步的药理和临床研究具有一定的参考价值。
Zhi-zi-chi decoction (ZZCD) is a classical formula widely used in Chinese clinical application. In the present study, a novel and efficient strategy has been developed for screening and identification of multiple constituents and their metabolites of ZZCD using ultra-high-performance liquid chromatography combined with triple time-of-flight mass spectrometry. The novel approach of an online data acquisition method dependent on multiple mass defect filter and dynamic background subtraction is combined with multiple data processing techniques. First, a total of 109 potential bioactive compounds were detected in ZZCD. Based on the same instrumental conditions, 100 compounds were found in rat biofluids after oral administration of ZZCD, including 61 original compounds of ZZCD as well as 39 metabolites. Conjugations with sulfate, glucuronate and amino acids were found as the predominant metabolic reaction of ZZCD. As more xenobiotics were detected in urine than those in bile were, it demonstrated that multiple components of ZZCD have undergone comprehensive renal excretion. This study reported the urinary and biliary excretion in rats after oral administration of ZZCD for the first time. The present study expands our knowledge about the constituents and metabolism of ZZCD, which could be very useful for further pharmacological and clinical studies of ZZCD.