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 Metabolite Profiling of Meridianin C In Vivo of Rat by UHPLC/Q-TOF MS

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Guozhe Zhang ◽  
Linxia Xiao ◽  
Liang Qi
Keyword(s):  
High Performance ◽  
Kinase Inhibitor ◽  
Solid Phase ◽  
Extraction Methods ◽  
Mass Spectral Fragmentation ◽  
Mass Spectral ◽  
Flight Mass Spectrometry ◽  
Fragmentation Patterns ◽  
Tof Ms

Meridianin C (MC), as a marine alkaloid, is a potent protein kinase inhibitor which exhibits good anticancer activity. However, the in vivo metabolism of MC has not been described to date. In this study, an ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UHPLC/Q-TOF MS) method is employed to investigate the in vivo metabolites of MC in rats. Plasma, bile, urine, and feces are collected after a single oral dose of MC. Protein precipitation, solid phase extraction (SPE), and ultrasonic extraction methods are used to prepare samples. Based on the mass spectral fragmentation patterns, elution order, and retrieving literatures, a total of 13 metabolites of MC were detected and tentatively identified, utilizing MetaboLynx software. The metabolic pathways of MC in rats include N- or O-glucuronidation, O-sulfation, N-hydroxylation, dihydroxylation, and trihydroxylation. The relative content of the metabolites in each kinds of biological samples is also evaluated. This study will help to understand the in vivo properties of MC for the future usage.

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 Purification, Identification, and Sensory Evaluation of Kokumi Peptides from Agaricus bisporus Mushroom

Foods ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 43 ◽  
Author(s):  
Tao Feng ◽  
Yang Wu ◽  
Zhiwen Zhang ◽  
Shiqing Song ◽  
Haining Zhuang ◽  
...  
Keyword(s):  
Liquid Chromatography ◽  
Sensory Evaluation ◽  
Agaricus Bisporus ◽  
High Performance ◽  
Solid Phase ◽  
Gel Permeation Chromatography ◽  
Ultra Performance Liquid Chromatography ◽  
Taste Intensity ◽  
Flight Mass Spectrometry ◽  
Tof Ms

Agaricus bisporus can enhance the umami and salty taste in chicken soup, and also has a high protein content, which indicates that there might be some kokumi taste compounds in this mushroom. Therefore, through ultrafiltration, gel permeation chromatography (GPC), and reverse phase-high performance liquid chromatography (RP-HPLC), some peptides in fresh Agaricus bisporus mushroom were isolated. Then, these peptides were identified by sensory evaluation and ultra performance liquid chromatography (UPLC) coupled quadruple time of flight mass spectrometry (Q-TOF-MS). The sensory evaluation results showed that the addition of aqueous extract isolated from Agaricus bisporus to model chicken broth did enhance chicken broth’s complexity, mouthfulness, and palatability. UPLC-Q-TOF-MS analysis found that Gly-Leu-Pro-Asp (Mw = 399.99) and Gly-His-Gly-Asp (Mw = 383.99) might act as key molecules to cause kokumi taste. In order to verify the kokumi taste of the above two peptides, they were synthesized by solid-phase synthesis and the taste properties of these two peptides were further characterized by descriptive sensory evaluation and taste intensity tests. This work indicated that it was feasible to produce kokumi peptides from Agaricus bisporus.

scholarly journals Development and Validation of QuEChERS Followed by UHPLC-ToF-MS Method for Determination of Multi-Mycotoxins in Pistachio Nuts

Molecules ◽  
2021 ◽  
Vol 26 (19) ◽  
pp. 5754
Author(s):  
Ana Rita Soares Mateus ◽  
Sílvia Barros ◽  
Angelina Pena ◽  
Ana Sanches Silva
Keyword(s):  
High Performance ◽  
Solid Phase ◽  
Quechers Method ◽  
Modified Silica ◽  
Modified Silica Gel ◽  
Flight Mass Spectrometry ◽  
High Lipid ◽  
Commission Regulation ◽  
Tof Ms

Pistachios are one of the types of tree nut fruits with the highest mycotoxin contamination, especially of aflatoxins, worldwide. This study developed a Quick, Easy, Cheap, Effective, Rugged, and Safe (QuEChERS) method that was followed by Ultra-High Performance Liquid Chromatography combined with Time-of-Flight Mass Spectrometry (UHPLC–ToF-MS) for the determination of mycotoxins in pistachios. Different approaches to dispersive solid phase extraction as a clean-up method for high lipid matrices were evaluated. For this, classic sorbents such as C18 (octadecyl-modified silica) and PSA (primary secondary amine), and new classes of sorbents, namely EMR-Lipid (enhanced matrix removal-lipid) and Z-Sep (modified silica gel with zirconium oxide), were used. The QuEChERS method, followed by Z-Sep d-SPE clean-up, provided the best analytical performance for aflatoxins (AFB1, AFB2, AFG1 and AFG2), ochratoxin A (OTA), zearalenone (ZEA), toxin T2 (T2) and toxin HT-2 (HT2) in pistachios. The method was validated in terms of linearity, sensitivity, repeatability, interday precision and recovery; it achieved good results according to criteria imposed by Commission Regulation (EC) no. 401/2006. The method was applied to real samples and the results show that pistachios that are available in Portuguese markets are safe from mycotoxins that are of concern to human health.

Sign in / Sign up

Export Citation Format

Share Document