Identification of the metabolites of n‐butylidenephthalide in rat and human liver microsomes by liquid chromatography–high‐resolution mass spectrometry

Abstract

n-Butylidenephthalide (NBDP) is one of the bioactive constituents originally isolated from Ligusticum chuanxiong Hort. The aim of this study was to study the metabolic profiles of NBDP in rat and human liver microsomes. NBDP was individually incubated with liver microsomes of rat and human at 37 C for 1 h and the samples incubated were analyzed by ultra-high-performance liquid chromatography combined with high-resolution mass spectrometry. The identities of the metabolites were identified by accurate masses, product ions and retention times. Under the current conditions, a total of 14 metabolites were detected and identified. M12, M13 and M14 were biosynthesized and unambiguously characterized by nuclear magnetic resonance spectroscopy. All the metabolites can be detected in rat liver microsomes, whereas in human liver microsomes, M1, M3, M4, M5, M6 and M7 were not detected. Our results demonstrated that the metabolic pathways of NBDP included hydroxylation, hydration, hydrolysis and glutathione conjugation. This study provides an overview of the metabolic profiles of NBDP in vitro, which is helpful to understand the action of this compound.

Characterization of diterpene metabolism in rats with ingestion of seed products from Euphorbia lathyris L. (Semen Euphorbiae and Semen Euphorbiae Pulveratum) using UHPLC‐Q‐Exactive MS

“…Although it is known that the chemical components in SE and SEP are absorbed across the intestinal barrier and rapidly removed by metabolic conversion, their metabolic products in vivo have not been fully characterized (Wang et al, 2020;Yang et al, 2021). Now, ultra-high-performance liquid chromatography-quadrupole-Exactive mass spectrometry (UHPLC-Q-Exactive MS) has become a routine technique for the detection and analysis of metabolites, especially for the identification of metabolites in a biological system or in complex samples (Chang et al, 2021;Feng et al, 2021;Lin et al, 2021;Xing et al, 2014;Zhao et al, 2021). To the best of our knowledge, there is no report on the pharmacokinetics of SE and SEP using UHPLC-Q-Exactive MS.…”

“…Now, ultra‐high‐performance liquid chromatography‐quadrupole‐Exactive mass spectrometry (UHPLC‐Q‐Exactive MS) has become a routine technique for the detection and analysis of metabolites, especially for the identification of metabolites in a biological system or in complex samples (Chang et al, 2021; Feng et al, 2021; Lin et al, 2021; Xing et al, 2014; Zhao et al, 2021). To the best of our knowledge, there is no report on the pharmacokinetics of SE and SEP using UHPLC‐Q‐Exactive MS.…”

A high‐resolution mass spectrometric method for identification and characterization of the in vitro metabolites of senkyunolide H

“…Several reports are available on the metabolism of phthalides, such as senkyunolide A, 8 ligustilide, 9 senkyunolide I, 10 and 3-butylidenephthalide. 11 However, to the best of our knowledge, there is no report on the metabolism of SNH. In early stage, in vitro models are frequently utilized to evaluate the metabolism of drugs, such as hepatocytes deriving from liver and retained most of drugmetabolizing enzymes, 12 which represents a powerful tool for metabolism study.…”

“…In particular, an early understanding of metabolite profiles in humans may increase drug safety that is of greatest regulatory and public health interest. Several reports are available on the metabolism of phthalides, such as senkyunolide A, 8 ligustilide, 9 senkyunolide I, 10 and 3‐butylidenephthalide 11 . However, to the best of our knowledge, there is no report on the metabolism of SNH.…”

Design, synthesis and bioactivity of a new class of antifungal amino acid‐directed phthalide compounds

“…However, butylidenephthalide is known for its medicinal properties in treating cardiac arrhythmias 10 and early dementia, 11 in which substance's hazard code is Xn (Harmful), and use in the field may pose a risk to non-target organisms. [12][13][14] Moreover, the conditions and steps involved in synthesizing the compound are complex. 15 Therefore, when designing and synthesizing target compounds, it is important to consider how to reduce toxicity and simplify synthesis steps while maintaining activity.…”