UPLC–ESI-Q-TOF/MS based metabolic profiling of protosappanin B in rat plasma, bile, feces, urine and intestinal bacteria samples

2021 ◽  
Vol 22 ◽  
Author(s):  
Wei-Ying Chen ◽  
Guang-Yan Liang ◽  
Zuo-Liang Zheng ◽  
Yun-Shan Wu ◽  
Fang-Fang Xu ◽  
...  
Keyword(s):  
Intestinal Bacteria ◽  
Rat Plasma ◽  
Caesalpinia Sappan ◽  
Promote Blood Circulation ◽  
Flight Mass Spectrometry ◽  
Glucuronide Conjugation ◽  
Glucose Conjugation ◽  
Phase Ii Metabolites ◽  
Rat Bile ◽  
Tof Ms

Background: Caesalpinia sappan L. is a traditional medicinal plant that is used to promote blood circulation and treat stroke in China. Protosappanin B (PTB) is a unique homoisoflavone compound isolated from Sappan Lignum (the heartwood of Caesalpinia sappan L). In a previous study, the metabolic fate of PTB remained unknown. Objective: To explore whether PTB is extensively metabolized, the metabolites of PTB in bile, plasma, urine, feces, and intestinal bacteria samples in rats were investigated. Method: The biosamples were investigated by ultraperformance liquid chromatography combined with time-of-flight mass spectrometry (UPLC-TOF-MS/MS) with MetabolitePilot software. Result: 28 metabolites were identified in the biosamples: 18 metabolites in rat bile, 8 in plasma, 20 in feces, 7 in urine and 2 in intestinal bacteria samples. Both phase I and phase II metabolites were observed. Metabolite conversion occurred via 9 proposed pathways: sulfate conjugation, glucuronide conjugation, bis-glucuronide conjugation, glucose conjugation, dehydration, oxidation, hydrolysis, methylation and hydroxymethylene loss. The metabolic pathways differed among biosamples and exhibited different distributions. Among these pathways, the most important were sulfate and glucuronide conjugation. Conclusion: The results showed that the small intestinal and biliary routes play an important role in the clearance and excretion of PTB. The main sites of metabolism in the PTB chemical structure were the phenolic hydroxyl and the side-chains on the eight-element ring.

scholarly journals An Accurate and Effective Method for Measuring Osimertinib by UPLC-TOF-MS and Its Pharmacokinetic Study in Rats

Molecules ◽  
2018 ◽  
Vol 23 (11) ◽  
pp. 2894 ◽  
Author(s):  
Song-Tao Dong ◽  
Ying Li ◽  
Hao-Tian Yang ◽  
Yin Wu ◽  
Ya-Jing Li ◽  
...  
Keyword(s):  
Matrix Effects ◽  
Internal Standard ◽  
Ultra Performance Liquid Chromatography ◽  
Rat Plasma ◽  
Analysis Method ◽  
T790m Mutation ◽  
Flight Mass Spectrometry ◽  
Relative Standard ◽  
New Generation ◽  
Tof Ms

Osimertinib, a new-generation inhibitor of the epidermal growth factor, has been used for the clinical treatment of advanced T790M mutation-positive tumors. In this research, an original analysis method was established for the quantification of osimertinib by ultra-performance liquid chromatography with time of flight mass spectrometry (UPLC-TOF-MS) in rat plasma. After protein precipitation with acetonitrile and sorafinib (internal standard, IS), they were chromatographed through a Waters XTerra MS C18 column. The mobile phase was acetonitrile and water (including 0.1% ammonia). The relative standard deviation (RSD) of the intra- and inter-day results ranged from 5.38 to 9.76% and from 6.02 to 9.46%, respectively, and the extraction recovery and matrix effects were calculated to range from 84.31 to 96.14% and from 91.46 to 97.18%, respectively. The results illustrated that the analysis method had sufficient specificity, accuracy and precision. Meanwhile, the UPLC-TOF-MS method for osimertinib was successfully applied into the pharmacokinetics of SD rats.

scholarly journals The Evaluation of Toxicity Induced by Psoraleae Fructus in Rats Using Untargeted Metabonomic Method Based on UPLC-Q-TOF/MS

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Yanyan Xu ◽  
Yiwei Zhao ◽  
Jiabin Xie ◽  
Xue Sheng ◽  
Yubo Li ◽  
...  
Keyword(s):  
Metabolic Pathways ◽  
Acid Metabolism ◽  
Safety Evaluation ◽  
Rat Plasma ◽  
Leguminous Plant ◽  
Control Group ◽  
Kidney Toxicity ◽  
Flight Mass Spectrometry ◽  
Liver And Kidney ◽  
Tof Ms

Psoraleae Fructus is the dry and mature fruit of leguminous plant Psoralea corylifolia L., with the activity of warming kidney and enhancing yang, warming spleen, and other effects. However, large doses can cause liver and kidney toxicity. Therefore, it is necessary to evaluate the toxicity of Psoraleae Fructus systematically. Although traditional biochemical indicators and pathological tests have been used to evaluate the safety of drug, these methods lack sensitivity and specificity, so a fast and sensitive analytical method is urgently needed. In this study, an ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) method was used to analyze the metabolic profiles of rat plasma. The changes of metabolites in plasma samples were detected by partial least squares-discriminant analysis (PLS-DA). Compared with the control group, after 7 days of administration, the pathological sections showed liver and kidney toxicity, and the metabolic trend was changed. Finally, 13 potential biomarkers related to the toxicity of Psoraleae Fructus were screened. The metabolic pathways involved were glycerol phospholipids metabolism, amino acid metabolism, energy metabolism, and so forth. The discovery of these biomarkers laid a foundation for better explaining the hepatotoxicity and nephrotoxicity of Psoraleae Fructus and provided a guarantee for its safety evaluation.

scholarly journals A Complete Study of Farrerol Metabolites Produced in Vivo and in Vitro

Molecules ◽  
2019 ◽  
Vol 24 (19) ◽  
pp. 3470
Author(s):  
Yin ◽  
Ma ◽  
Liang ◽  
Wang ◽  
Sun ◽  
...  
Keyword(s):  
High Performance ◽  
Liver Microsomes ◽  
Rat Liver Microsomes ◽  
Flight Mass Spectrometry ◽  
Multiple Data ◽  
Glucuronide Conjugation ◽  
Complete Study ◽  
Glucose Conjugation

Although farrerol, a characteristically bioactive constituent of Rhododendron dauricum L., exhibits extensive biological and pharmacological activities (e.g., anti-oxidant, anti-immunogenic, and anti-angiogenic) as well as a high drug development potential, its metabolism remains underexplored. Herein, we employed ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry coupled with multiple data post-processing techniques to rapidly identify farrerol metabolites produced in vivo (in rat blood, bile, urine and feces) and in vitro (in rat liver microsomes). As a result, 42 in vivo metabolites and 15 in vitro metabolites were detected, and farrerol shown to mainly undergo oxidation, reduction, (de)methylation, glucose conjugation, glucuronide conjugation, sulfate conjugation, N-acetylation and N-acetylcysteine conjugation. Thus, this work elaborates the metabolic pathways of farrerol and reveals the potential pharmacodynamics forms of farrerol.

Identification of poliumoside metabolites in rat plasma, urine, bile, and intestinal bacteria with UPLC/Q-TOF-MS

2018 ◽  
Vol 16 (11) ◽  
pp. 871-880 ◽  
Author(s):  
Hao QIAN ◽  
Fang-Jun YU ◽  
Dan-Yi LU ◽  
Bao-Jian WU ◽  
Xing-Wang ZHANG ◽  
...  
Keyword(s):  
Intestinal Bacteria ◽  
Rat Plasma ◽  
Tof Ms

Identification of in vivo metabolites of a potential anti-tumor drug candidate AMAC, in rat plasma, urine and feces samples using UHPLC/Q-TOF /MS/MS

2019 ◽  
Vol 16 ◽  
Author(s):  
Caixia Dou ◽  
Minghai Tang ◽  
Yuanyuan Xia ◽  
Linyu Yang ◽  
Xiang Qiu ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
High Performance ◽  
Rat Plasma ◽  
Drug Candidate ◽  
Two Phase ◽  
Colchicine Binding Site ◽  
Phase Ii Metabolites ◽  
Pharmaceutical Agents ◽  
Tof Ms

: Natural products targeting the microtubule system comprise a large portion of current-day pharmaceutical agents, most notably in the area of cancer therapy. 4-((3-amino-4-methoxyphenyl) amino)-2H-coumarin (AMAC), derived from coumarin, demonstrated excellent anti-proliferative activity through directly binding to the colchicine-binding site in β-tubulin, suggesting that it could be a potential drug candidate for anti-tumor drug research and development. Identification and structural characterization of metabolites is a critical step of both drug discovery and development. In this study, an efficient and sensitive method using Ultra High-Performance Liquid Chromatography coupled with Quadrupole Time of Flight tandem Mass Spectrometry (UHPLC/Q-TOF/MS/MS) was successfully established and applied to identify the in vivo metabolites in plasma, urine and feces samples of rats after intravenous administration of AMAC with a single dose of 10 mg/kg. A total two phase I and six phase II metabolites were detected or tentatively identified in plasma, urine and feces, indicating the prominent metabolic pathways were glucuronidation, demethylation and hydroxylation, respectively. In addition, chemical synthesis was used to accurately confirm the structure of M3, since its structure might be ambiguous judging from the results of mass spectrometry. The present study provides important information on the metabolites of AMAC in vivo for the first time, which would be helpful for the further development of AMAC.

scholarly journals A Study of the Identification, Fragmentation Mode and Metabolic Pathways of Imatinib in Rats Using UHPLC-Q-TOF-MS/MS

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Sijiang Liu ◽  
Zhaojin Yu
Keyword(s):  
Metabolic Pathways ◽  
High Performance ◽  
Kinase Inhibitor ◽  
Solid Phase ◽  
Rat Plasma ◽  
Amide Bond ◽  
Catalytic Dehydrogenation ◽  
Fragmentation Pattern ◽  
Flight Mass Spectrometry ◽  
Tof Ms

In this study, The metabolites, metabolic pathways, and metabolic fragmentation mode of a tyrosine kinase inhibitor- (TKI-) imatinib in rats were investigated. The samples for analysis were pretreated via solid-phase extraction, and the metabolism of imatinib in rats was studied using ultra-high-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS). Eighteen imatinib metabolites were identified in rat plasma, 21 in bile, 18 in urine, and 12 in feces. Twenty-seven of the above compounds were confirmed as metabolites of imatinib and 9 of them were newly discovered for the first time. Oxidation, hydroxylation, dealkylation, and catalytic dehydrogenation are the main metabolic pathways in phase I. For phase II, the main metabolic pathways were N-acetylation, methylation, cysteine, and glucuronidation binding. The fragment ions of imatinib and its metabolites were confirmed to be produced by the cleavage of the C-N bond at the amide bond. The newly discovered metabolite of imatinib was identified by UHPLC-Q-TOF-MS/MS. The metabolic pathway of imatinib and its fragmentation pattern were summarized. These results could be helpful to study the safety of imatinib for clinical use.

scholarly journals Analyses of Lipid A Diversity in Gram-Negative Intestinal Bacteria Using Liquid Chromatography–Quadrupole Time-of-Flight Mass Spectrometry

Metabolites ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 197
Author(s):  
Nobuyuki Okahashi ◽  
Masahiro Ueda ◽  
Fumio Matsuda ◽  
Makoto Arita
Keyword(s):  
Mass Spectrometry ◽  
Immune Response ◽  
Liquid Chromatography ◽  
Mammalian Cells ◽  
Lipid A ◽  
Acyl Chain ◽  
Time Of Flight ◽  
Intestinal Bacteria ◽  
Gram Negative ◽  
Flight Mass Spectrometry

Lipid A is a characteristic molecule of Gram-negative bacteria that elicits an immune response in mammalian cells. The presence of structurally diverse lipid A types in the human gut bacteria has been suggested before, and this appears associated with the immune response. However, lipid A structures and their quantitative heterogeneity have not been well characterized. In this study, a method of analysis for lipid A using liquid chromatography–quadrupole time-of-flight mass spectrometry (LC-QTOF/MS) was developed and applied to the analyses of Escherichia coli and Bacteroidetes strains. In general, phosphate compounds adsorb on stainless-steel piping and cause peak tailing, but the use of an ammonia-containing alkaline solvent produced sharp lipid A peaks with high sensitivity. The method was applied to E. coli strains, and revealed the accumulation of lipid A with abnormal acyl side chains in knockout strains as well as known diphosphoryl hexa-acylated lipid A in a wild-type strain. The analysis of nine representative strains of Bacteroidetes showed the presence of monophosphoryl penta-acylated lipid A characterized by a highly heterogeneous main acyl chain length. Comparison of the structures and amounts of lipid A among the strains suggested a relationship between lipid A profiles and the phylogenetic classification of the strains.

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