UPLC-QTOF-MS/MS based screening and identification of the metabolites in rat bile after oral administration of imperatorin

Song, Guohe; Jin, Miaomiao; Du, Yingfeng; Cao, Liang; Xu, Huijun

doi:10.1016/j.jchromb.2016.04.007

Cited by 31 publications

(33 citation statements)

References 19 publications

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“…This information is valuable for optimizing the structure of lead compounds, selecting drugs with high metabolic stability and exploring the drugs’ possible pharmacological or toxicological mechanisms. High‐performance liquid chromatography–high‐resolution mass spectrometry (HPLC–HRMS) (Song, Jin, Du, Cao, & Xu, ) has high resolution, accuracy and sensitivity, is fast scanning and involves multistage mass spectrometry (MS n ). It is a powerful tool for analysing drug metabolites and can be used to obtain HRMS and MS n data from potential metabolic products in biological samples using a simple, universal collection method.…”

Section: Introductionmentioning

confidence: 99%

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Rapid detection and structural characterization of verapamil metabolites in rats by UPLC–MSE and UNIFI platform

Zhu

Wan

Cheng

et al. 2019

Biomedical Chromatography

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High‐resolution mass spectrometry (HRMS) is an important technology for studying biotransformations of drugs in biological systems. In order to process complex HRMS data, bioinformatics, including data‐mining techniques for identifying drug metabolites from liquid chromatography/high‐resolution mass spectrometry (LC/HRMS) or multistage mass spectrometry (MSn) datasets as well as elucidating the detected metabolites’ structure by spectral interpretation software, are important tools. Data‐mining technologies have widely been used in drug metabolite identification, including mass defect filters, product ion filters, neutral‐loss filters, control sample comparisons and extracted ion chromatographic analysis. However, the metabolites identified by current different technologies are not the same, indicating the importance of technique integration for efficient and complete identification of metabolic products. In this study, a universal, high‐throughput workflow for identifying and verifying metabolites by applying the drug metabolite identification software UNIFI is reported, to study the biotransformation of verapamil in rats. A total of 71 verapamil metabolites were found in rat plasma, urine and faeces, including two metabolites that have not been reported in the literature. Phase I metabolites of verapamil were identified as N‐demethylation, O‐demethylation, N‐dealkylation and oxidation and dehydrogenation metabolites; phase II metabolites were mainly glucuronidation and sulfate conjugates, indicating that UNIFI software could be effective and valuable in identifying drug metabolites.

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Section: Introductionmentioning

confidence: 99%

“…Therefore, approaches to efficiently and comprehensively identify the information of interest as well as to analyse metabolic products in post‐processing, have become one of the key issues in HPLC–HRMS applications. (Gao, Wu, & Feng, ; Martano, Mugoni, Dal Bello, Santoro, & Medana, ; Scheidweiler, Jarvis, & Huestis, ; Song et al, )…”

Section: Introductionmentioning

confidence: 99%

Rapid detection and structural characterization of verapamil metabolites in rats by UPLC–MSE and UNIFI platform

Zhu

Wan

Cheng

et al. 2019

Biomedical Chromatography

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“…We determined that they were demethylated to carboxylic acid metabolites based on the previous reports (Huo et al, 2015). (Qiao et al, 2013 The diagnostic product ion at m/z 67.0563 was also obtained, indicating that M24 was a dehydrogen metabolite of cnidilin and the dehydrogen position was in the isopentenyl group located in the side chain (Song, Jin, Do, Cao, & Xu, 2016).…”

Section: Identification Of Metabolitesmentioning

confidence: 80%

“…The quasi‐molecular ion lost molecules of C 5 H 6 and CH 3 , yielding the typical fragment ions at m/z 233.0446 and 218.0213, with the peaks appearing at m/z 190.0270, 173.0233, 162.0309 and 145.0286 by successive losses of CO. The diagnostic product ion at m/z 67.0563 was also obtained, indicating that M24 was a dehydrogen metabolite of cnidilin and the dehydrogen position was in the isopentenyl group located in the side chain (Song, Jin, Do, Cao, & Xu, ).…”

Section: Resultsmentioning

confidence: 99%

UHPLC‐Q‐TOF‐MS/MS‐based screening and characterization of metabolites of cnidilin in human liver microsomes

Lin

Zhang

Liao

et al. 2017

Biomedical Chromatography

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Cnidilin is an active natural furocoumarin ingredient originating from well-known traditional Chinese medicine Radix Angelicae Dahuricae. In the present study, an efficient approach was developed for the screening and identification of cnidilin metabolites using ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry. In this approach, an on-line data acquisition method multiple mass defect filter combined with dynamic background subtraction was developed to trace all probable metabolites. Based on this analytical strategy, a total of 24 metabolites of cnidilin were detected in human liver microsomal incubation samples and the metabolic pathways were proposed. The results indicated that oxidation was the main biotransformation route for cnidilin in human liver microsomes. In addition, the specific cytochrome P450 (CYP) enzymes involved in the metabolism of cnidilin were identified using chemical inhibition and CYP recombinant enzymes. The results showed that CYP1A2 and CYP3A4 might be the major enzymes involved in the metabolism of cnidilin in human liver microsomes. The relationship between cnidilin and the CYP450 enzymes could provide us a theoretical basis of the pharmacological mechanism.

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“…The metabolite study is an essential part for the drug discovery and development. Meanwhile, it is helpful to understand the metabolic characteristics, efficacy and toxicity . However, the studies of HDC have only been reported in pharmacokinetics and quantitative determination .…”

Section: Introductionmentioning

confidence: 99%

Characterisation of hederacoside C metabolites using ultrahigh‐performance liquid chromatography quadrupole Orbitrap mass spectrometry based on automatic fragment ion search

Jiang

Yang

Zhang

et al. 2020

Phytochemical Analysis

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Introduction Hederacoside C (HDC) is a bioactive natural triterpenoid saponins constituent originating from traditional Chinese medicines, playing an important role in the treatment of acute respiratory infections and chronic inflammatory bronchitis. Meanwhile, it is recognised by Korea as a botanical drug. Objectives In order to develop an integrated template approach to analysing screening and identification of the metabolites of traditional Chinese medicines. This study will provide available information for further pharmaceutical studies of HDC and other triterpene saponins. Methodology An analysis strategy based on ultrahigh‐performance liquid chromatography quadrupole Orbitrap mass spectrometry (UHPLC‐Q‐Orbitrap‐MS) technique combined with automatic fragment ion search (FISh) was firstly exploited for the characterisation metabolites of HDC in vivo and in vitro. Accurate full mass scan combined with an on‐line FISh annotations approach was developed to rapidly identify all the potential metabolites of HDC. Furthermore, FISh accurately located the structure of the target compound in a large number of mass spectral data. Results A total of 34 metabolites were detected and tentatively identified by analysing comprehensive biological samples. The results clearly demonstrated that HDC underwent general metabolic reactions including dealkylation, reduction, oxidation, desaturation, dehydration, cysteine conjugation, GSH conjugation, taurine conjugation, and glycine conjugation to produce 26 phase I and eight phase II metabolites. Conclusion In the present study, UHPLC‐Q‐Exactive Orbitrap MS technique combined with FISh provided a rapid and efficient platform to characterise metabolites of HDC in vivo and in vitro. The proposed method could develop an integrated template approach to screen and identify the constituents and metabolites of traditional Chinese medicines.

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UPLC-QTOF-MS/MS based screening and identification of the metabolites in rat bile after oral administration of imperatorin

Cited by 31 publications

References 19 publications

Rapid detection and structural characterization of verapamil metabolites in rats by UPLC–MSE and UNIFI platform

Rapid detection and structural characterization of verapamil metabolites in rats by UPLC–MSE and UNIFI platform

UHPLC‐Q‐TOF‐MS/MS‐based screening and characterization of metabolites of cnidilin in human liver microsomes

Characterisation of hederacoside C metabolites using ultrahigh‐performance liquid chromatography quadrupole Orbitrap mass spectrometry based on automatic fragment ion search

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