Identification of the metabolites of isochlorogenic acid A in rats by UHPLC-Q-Exactive Orbitrap MS

Abstract

Content: Isochlorogenic acid A, one of the main components of Duhaldea nervosa (Wallich ex Candolle) A. Anderberg (Asteraceae), is a folk medicine used to treat a variety of diseases including fracture and rheumatoid arthritis. Despite its widespread use, the metabolism of isochlorogenic acid A in vivo has not been fully studied. Objective: An analytical strategy based on UHPLC-Q-Exactive Orbitrap MS is proposed for the detection and identification of the metabolites of isochlorogenic acid A in rats. Materials and methods: Six male Sprague-Dawley rats (180 ± 20 g) were randomly divided into two groups. Then, blood and tissue samples were obtained after oral administration of isochlorogenic acid A (200 mg/kg). All the samples were pre-treated by the Solid Phase Extraction (SPE) method. Next, the samples were analysed by UHPLC-Q-Exactive Orbitrap MS. Finally, the metabolites were identified based on the metabolomic workflow template. Results: A total of 33 metabolites were identified in rat plasma, with 30 of them being reported for the first time. The distribution of all metabolites in tissues was first investigated, three of them were widely distributed in liver, lungs, and kidneys. The corresponding reactions including methylation, hydrolysis, sulphate conjugation, glucuronide conjugation, as well as their composite reactions, are reported in this study. Discussion and conclusions: This method has wide-scale application prospects in the identification of metabolites. Considering that limited research has been conducted in this area, this study proposes metabolic pathways to further understand mechanisms of isochlorogenic acid A and the forms that are truly effective in vivo.

Systemic chemical characterization of Lemna minor by UHPLC‐Q‐Exactive Orbitrap MS coupled with parallel reaction monitoring

“…Compound 13 showed fragment ions at m/z 110.0602 [M + H‐CO] + and m/z 94.0655 [M + H‐CO‐O] − in the MS/MS 2 spectrum, which was consistent with data in the literature, 13 and was therefore identified as trigonelline. Compounds 74, 78, and 80 all showed the precursor ion at m/z 144.0808 [M + H] + , and the MS 2 fragment ion at m/z 84.960, so compounds 74, 78, and 80 were identified as isomers of naphthylamine 13 . Compound 101 was identified as trihydroxy‐octadecenoic acid in the literature 19 .…”

“…Compounds 2, 5, and 13 show [M + H] + ions at m/z 104.1070, 266.1234, and 138.0550; among them, compound 2 produced a fragment ion of m/z 60.0817 [M‐C 2 H 4 O] + ; therefore, it was identified as choline 13 ; the fragment ions of compound 5 were m/z 248.1125 [M + H‐H 2 O] + , m/z 230.1021 [M + H‐2H 2 O] + , and m/z 116.0707 [M + H‐2H 2 O‐CH 2 ] + ; it was identified as GABA‐O‐Glucose 10 . Compound 13 showed fragment ions at m/z 110.0602 [M + H‐CO] + and m/z 94.0655 [M + H‐CO‐O] − in the MS/MS 2 spectrum, which was consistent with data in the literature, 13 and was therefore identified as trigonelline. Compounds 74, 78, and 80 all showed the precursor ion at m/z 144.0808 [M + H] + , and the MS 2 fragment ion at m/z 84.960, so compounds 74, 78, and 80 were identified as isomers of naphthylamine 13 .…”

Unraveling the mystery of efficacy in Chinese medicine formula: New approaches and technologies for research on pharmacodynamic substances

“…Finally, metabolic pathways of metabolites in vivo including 1-phase metabolism and 2-phase metabolism were characterized. Under the strategy, many compound formulas have been studied for blood entry components, such as Xialian Capsule ( Li et al, 2018 ), Wutou decoction ( Cheng et al, 2021 ), Dan Zhi Tablet ( Mi et al, 2019 ), Sanmiao Wan ( Ma et al, 2021b ), isochlorogenic acid A ( Gong et al, 2020 ), Dahuang Zhechong pill ( Ni et al, 2020 ), Smilacis Glabrae Rhizoma ( Gegentana et al, 2020 ). In the current research, Zhang et al ( Zhang et al, 2019f ) and Zhu et al ( Zhu et al, 2021 ) combined serum medicinal chemistry to establish an innovative herbal pharmacomics strategy capable to discover effective substances.…”

Comprehensive characterization of multiple components of Ziziphus jujuba Mill using UHPLC‐Q‐Exactive Orbitrap Mass Spectrometers

“…It shows a wide range of analysis and strong separation ability and yields reliable qualitative analysis results (Liang et al, 2022 ). In this study, the UHPLC‐Q‐Exactive Orbitrap MS combined with PRM was adopted to characterize the compounds in Z. jujuba (Gong et al, 2020 ; Qin et al, 2021 ). Finally, 295 compounds were identified in Z. jujuba .…”