National Center of Mass Spectrometry in Changchun and Jilin Province Key Laboratory of Chinese Medicine Chemistry and Mass Spectrometry and Chemical Biology Laboratory, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China; University of Science and Technology of China, Hefei, 230026, China.
National Center of Mass Spectrometry in Changchun and Jilin Province Key Laboratory of Chinese Medicine Chemistry and Mass Spectrometry and Chemical Biology Laboratory, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China.
J Pharm Biomed Anal. 2019 Feb 20;165:173-181. doi: 10.1016/j.jpba.2018.12.005. Epub 2018 Dec 5.
In this study, a novel analysis strategy for progressively targeted screening and characterization of drug ingredients from in vitro to in vivo was proposed based on ultra-high performance liquid chromatography-tandem mass spectrometry for comprehensive characterization of in vivo metabolic profile of Polygalae radix (PR). First, an in vitro chemical profile of PR was described with the assistance of UNIFI™ software. The characteristic neutral small molecule losses were summarized to distinguish different chemical structures in the PR extract. Second, the in vitro intestinal microflora metabolism model was applied to describe an in vitro metabolic profile of the main ingredients of PR. The metabolic rule and metabolites were integrated for subsequent targeted screening of metabolites in vivo. Finally, an integrated strategy was established and applied to screen and characterize the major absorbed components in vivo, including blood, urine, brain, feces, and liver, based on the prototypes and metabolic rules obtained in vitro. As a result, in vitro and in vivo metabolic profiles of PR were effectively depicted. A total of 136 compounds were isolated and identified from the crude extract in vitro, and 12 compounds were reported for the first time based on the proposed fragmentations. A total of 13, 32, and 3 compounds were identified and characterized in the dosed plasma, liver, and brain, respectively. A total of 40 and 73 compounds were identified in urine and feces, respectively. This strategy not only provided a comprehensive insight into the chemical and metabolic profiles of PR but also presented a new perspective for the discovery of new drugs for medicinal application.
在这项研究中，提出了一种基于超高效液相色谱-串联质谱的新型分析策略，用于逐步靶向筛选和表征药物成分，从体外到体内，以全面描述远志的体内代谢特征。首先，借助 UNIFI™软件描述了远志的体外化学特征。总结了特征性中性小分子的损失，以区分远志提取物中的不同化学结构。其次，应用体外肠道微生物代谢模型来描述远志主要成分的体外代谢特征。整合代谢规律和代谢物，以便后续在体内靶向筛选代谢物。最后，基于体外获得的原型和代谢规律，建立了一种综合策略，用于筛选和表征体内的主要吸收成分，包括血液、尿液、脑、粪便和肝脏。结果，有效地描绘了远志的体外和体内代谢特征。从体外粗提物中分离鉴定了 136 种化合物，其中 12 种化合物根据提出的碎片首次报道。在给药血浆、肝脏和大脑中分别鉴定和表征了 13、32 和 3 种化合物。在尿液和粪便中分别鉴定出 40 和 73 种化合物。该策略不仅提供了对远志的化学和代谢特征的全面了解，而且为药物应用的新药发现提供了新的视角。
