scholarly journals Quantification and Metabolite Identification of Sulfasalazine in Mouse Brain and Plasma Using Quadrupole-Time-of-Flight Mass Spectrometry

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 1179
Author(s):  
Jangmi Choi ◽  
Min-Ho Park ◽  
Seok-Ho Shin ◽  
Jin-Ju Byeon ◽  
Byeong ill Lee ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Central Nervous System ◽  
Mouse Brain ◽  
Metabolite Identification ◽  
Beneficial Effects ◽  
Flight Mass Spectrometry ◽  
Brain Exposure ◽  
Intravenous And Oral Administration ◽  
The Brain

Sulfasalazine (SAS), an anti-inflammatory drug with potent cysteine/glutamate antiporter system xc-(SXC) inhibition has recently shown beneficial effects in brain-related diseases. Despite many reports related to central nervous system (CNS) effect of SAS, pharmacokinetics (PK) and metabolite identification studies in the brain for SAS were quite limited. The aim of this study was to investigate the pharmacokinetics and metabolite identification of SAS and their distributions in mouse brain. Using in vivo brain exposure studies (neuro PK), the PK parameters of SAS was calculated for plasma as well as brain following intravenous and oral administration at 10 mg/kg and 50 mg/kg in mouse, respectively. In addition, in vivo metabolite identification (MetID) studies of SAS in plasma and brain were also conducted. The concentration of SAS in brain was much lower than that in plasma and only 1.26% of SAS was detected in mouse brain when compared to the SAS concentration in plasma (brain to plasma ratio (%): 1.26). In the MetID study, sulfapyridine (SP), hydroxy-sulfapyridine (SP-OH), and N-acetyl sulfapyridine (Ac-SP) were identified in plasma, whereas only SP and Ac-SP were identified as significant metabolites in brain. As a conclusion, our results suggest that the metabolites of SAS such as SP and Ac-SP might be responsible for the pharmacological effect in brain, not the SAS itself.

scholarly journals Brain Targeting of anti-HIV Nucleosides: in vitro and in vivo Evaluation of 6-chloro-2′,3′-dideoxypurine, a Lipophilic Prodrug of 2′,3′-dideoxyinosine

1994 ◽  
Vol 5 (5) ◽  
pp. 304-311 ◽  
Author(s):  
K. J. Doshi ◽  
F. D. Boudinot ◽  
J. M. Gallo ◽  
R. F. Schinazi ◽  
C. K. Chu
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Oral Administration ◽  
Intravenous Administration ◽  
Brain Targeting ◽  
The Central Nervous System ◽  
Intravenous And Oral Administration ◽  
The Brain

Lipophilic 6-halo-2′,3′-dideoxypurine nucleosides may be useful prodrugs for the targeting of 2′,3′-dideoxyinosine (ddl) to the central nervous system. The purpose of this study was to evaluate the potential effectiveness of 6-chloro-2′,3′-dideoxypurine (6-CI-ddP) for the targeting of ddl to the brain. In vitro studies indicated that the adenosine deaminase-mediated biotransformation of 6-CI-ddP to ddl was more rapid in mouse brain homogenate than in mouse serum. The brain distribution of 6-CI-ddP and ddl was assessed in vivo in mice following intravenous and oral administration of the prodrug or parent drug. Brain concentrations of ddl were similar after intravenous administration of 6-CI-ddP or ddl. However, after oral administration of the 6-CI-ddP prodrug, significantly greater concentrations of ddl were seen in the brain compared to those found after oral administration of ddl. The brain:serum AUG ratio (expressed as a percentage) of ddl after intravenous administration of 50 mg kg−1 of the active nucleoside was 3%. Following oral administration of 250 mg kg−1 ddl, low concentrations of ddl were detected in the brain. Brain:serum AUC ratios following intravenous and oral administration of the prodrug 6-CI-ddP were 19–25%. Thus, brain:serum AUC ratios were 6- to 8-fold higher after prodrug administration than those obtained after administration of the parent nucleoside. Oral administration of 6-CI-ddP yielded concentrations of ddl in the brain similar to those obtained following intravenous administration. The results of this study provide further evidence that 6-CI-ddP may be a useful prodrug for delivering ddl to the central nervous system, particularly after oral administration.

scholarly journals Metabolite identification of ursolic acid in mouse plasma and urine after oral administration by ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry

RSC Advances ◽  
2018 ◽  
Vol 8 (12) ◽  
pp. 6532-6539 ◽  
Author(s):  
Xueyan Hu ◽  
Yunbing Shen ◽  
Shengnan Yang ◽  
Wei Lei ◽  
Cheng Luo ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
Oral Administration ◽  
Ursolic Acid ◽  
High Performance ◽  
Metabolite Identification ◽  
Flight Mass Spectrometry ◽  
Metabolism Study

First report on metabolism study of ursolic acid (UA) in vivo of mice.

scholarly journals Investigation of the Effect of Rice Wine on the Metabolites of the Main Components of Herbal Medicine in Rat Urine by Ultrahigh-Performance Liquid Chromatography-Quadrupole/Time-of-Flight Mass Spectrometry: A Case Study onCornus officinalis

2013 ◽  
Vol 2013 ◽  
pp. 1-10
Author(s):  
Gang Cao ◽  
Hao Cai ◽  
Xianke Yue ◽  
Sicong Tu ◽  
Baochang Cai ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Herbal Medicine ◽  
Rice Wine ◽  
Rat Urine ◽  
Flight Mass Spectrometry ◽  
Cornus Officinalis ◽  
Ultrahigh Performance Liquid Chromatography ◽  
Main Components

Ultrahigh-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (UPLC-QTOF/MS) was developed for rapid and sensitive analysis of the effect of rice wine on the metabolites of the main components of herbal medicine in rat urine. UsingCornus officinalisas a model of herbal medicine, the metabolite profiles of crude and processed (steaming the crude drug presteeped in rice wine)Cornus officinalisextracts in rat urine were investigated. The metabolites ofCornus officinaliswere identified by using dynamic adjustment of the fragmentor voltage to produce structure-relevant fragment ions. In this work, we identified the parent compounds and metabolites of crude and processedCornus officinalisin rats. In total, three parent compounds and seventeen new metabolites ofCornus officinaliswere found in rats. The contents of the parent compounds and metabolitesin vivovaried significantly after intragastric (i.g.) administration of aqueous extracts of crude and processedCornus officinalis. Data from this study suggests that UPLC-QTOF/MS could be used as a potential tool for uncovering the effects of excipients found in the metabolites of the main components of herbal medicine,in vivo, to predict and discover the processing mechanisms of herbal medicine.

scholarly journals Imaging Sterols and Oxysterols in Mouse Brain Reveals Distinct Spatial Cholesterol Metabolism

2018 ◽  
Author(s):  
Eylan Yutuc ◽  
Roberto Angelini ◽  
Mark Baumert ◽  
Natalia Mast ◽  
Irina Pikuleva ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Mouse Brain ◽  
Brain Function ◽  
Mass Spectrometry Imaging ◽  
Cholesterol Metabolism ◽  
Biologically Active ◽  
Wild Type ◽  
Tissue Slices ◽  
The Brain

AbstractDysregulated cholesterol metabolism is implicated in a number of neurological disorders. Many sterols, including cholesterol and its precursors and metabolites, are biologically active and important for proper brain function. However, spatial cholesterol metabolism in brain and the resulting sterol distributions are poorly defined. To better understand cholesterol metabolism in situ across the complex functional regions of brain, we have developed on-tissue enzyme-assisted derivatisation in combination with micro-liquid-extraction for surface analysis and liquid chromatography - mass spectrometry to image sterols in tissue slices (10 µm) of mouse brain. The method provides sterolomic analysis at 400 µm spot diameter with a limit of quantification of 0.01 ng/mm2. It overcomes the limitations of previous mass spectrometry imaging techniques in analysis of low abundance and difficult to ionise sterol molecules, allowing isomer differentiation and structure identification. Here we demonstrate the spatial distribution and quantification of multiple sterols involved in cholesterol metabolic pathways in wild type and cholesterol 24S-hydroxylase knock-out mouse brain. The technology described provides a powerful tool for future studies of spatial cholesterol metabolism in healthy and diseased tissues.SignificanceThe brain is a remarkably complex organ and cholesterol homeostasis underpins brain function. It is known that cholesterol is not evenly distributed across different brain regions, however, the precise map of cholesterol metabolism in the brain remains unclear. If cholesterol metabolism is to be correlated with brain function it is essential to generate such a map. Here we describe an advanced mass spectrometry imaging platform to reveal spatial cholesterol metabolism in situ at 400 µm resolution on 10 µm tissue slices from mouse brain. We mapped, not only cholesterol, but also other biologically active sterols arising from cholesterol turnover in both wild type and mice lacking cholesterol 24-hydroxylase (Cyp46a1), the major cholesterol metabolising enzyme.

Cannabinoid effects on adenylate cyclase and phosphodiesterase activities of mouse brain

1977 ◽  
Vol 55 (4) ◽  
pp. 934-942 ◽  
Author(s):  
Thomas W. Dolby ◽  
Lewis J. Kleinsmith
Keyword(s):  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Mouse Brain ◽  
Biogenic Amine ◽  
Specific Activity ◽  
Intraperitoneal Administration ◽  
The Brain

The experiments presented in this paper examine the mechanisms underlying the ability of cannabinoids to alter the in vivo levels of cyclic adenosine 3′,5′-monophosphate (cyclic AMP) in mouse brain. It was found that changes in cyclic AMP levels are a composite result of direct actions of cannabinoids on adenylate cyclase (EC 4.6.1.1) activity and indirect actions involving the potentiation or inhibition of biogenic amine induced activity of adenylate cyclase. Furthermore, the long-term intraperitoneal administration of 1-(−)-Δ-tetrahydrocannabinol to mice produced a form of phosphodiesterase (EC 3.1.4.17) in the brain whose activity is not stimulated by Ca2+, although its basal specific activity is similar to that of control animals. In vitro, the presence of the cannabinoids caused no significant changes in activity of brain PDE at the concentrations tested. Some correlations are presented which imply that many of the observed behavioral and physiological actions of the cannabinoids in mammalian organisms may be mediated via cyclic AMP mechanisms.

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