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Metabolic profiling of ligustilide and identification of the metabolite in rat and human hepatocytes by liquid chromatography combined with high‐resolution mass spectrometry
Author(s) -
Tao Simei,
Li Huidi,
Liu Jie
Publication year - 2020
Publication title -
journal of separation science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.72
H-Index - 102
eISSN - 1615-9314
pISSN - 1615-9306
DOI - 10.1002/jssc.202000951
Subject(s) - chemistry , metabolite , chromatography , mass spectrometry , hydroxylation , metabolic pathway , liquid chromatography–mass spectrometry , metabolomics , tandem mass spectrometry , metabolism , biochemistry , enzyme
Ligustilide is one of the most abundant bioactive ingredients in Rhizoma Chuanxiong that has been widely prescribed for medicinal purposes in China. To better understand the disposition and action of ligustilide, it is necessary to investigate the metabolic profiles. The in vitro metabolism was elucidated through incubating ligustilide with human and rat hepatocytes at 37°C. The incubation samples were collected at predefined time points to determine the metabolic stability. Upon metabolite identification and profiling, the incubation samples were analyzed by ultra‐high‐performance liquid chromatography combined with diode array detector and high‐resolution mass spectrometry. The structures of the metabolites were characterized based on their mass spectrometry spectra, tandem mass spectrometry spectra, and fragmentation patterns. Ligustilide showed fast metabolism with high intrinsic clearance both in rat and human hepatocyte incubations. The half‐lives of ligustilide in rat and human hepatocyte incubations were 8.0 and 15.0 min, respectively. Most of the parent (>90%) was biotransformed into the metabolites. Among these metabolites, M1 (senkyunolide I) was the major metabolite both in rat and human hepatocytes with the percentage of 42 and 70%, respectively. The metabolic pathways of ligustilide included epoxidation, epoxide hydrolysis, aromatization, hydroxylation, and glutathionylation. This work provided an overview of the metabolic profiles of ligustilide, which would be helpful for us to understand the action of this compound.