scholarly journals In vivo drug metabolite identification in preclinical ADME studies by means of UPLC/TWIMS/high resolution-QTOF MSE and control comparison: cost and benefit of vehicle-dosed control samples

Xenobiotica ◽  
2016 ◽  
Vol 46 (10) ◽  
pp. 922-930 ◽  
Author(s):  
Lukas Fiebig ◽  
Ralf Laux ◽  
Rudolf Binder ◽  
Thomas Ebner
Keyword(s):  
High Resolution ◽  
Metabolite Identification ◽  
Cost And Benefit ◽  
Drug Metabolite ◽  
Control Comparison ◽  
And Control ◽  
Control Samples

scholarly journals Pharmacokinetics and Novel Metabolite Identification of Tartary Buckwheat Extracts in Beagle Dogs Following Co-Administration with Ethanol

Pharmaceutics ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 525
Author(s):  
Yuancai Liu ◽  
Jun Gan ◽  
Wanyu Liu ◽  
Xin Zhang ◽  
Jian Xu ◽  
...  
Keyword(s):  
High Resolution ◽  
Pharmacokinetic Study ◽  
Oral Bioavailability ◽  
Metabolite Identification ◽  
Tartary Buckwheat ◽  
Beagle Dogs ◽  
Beagle Dog ◽  
In Vivo Pharmacokinetics ◽  
Resolution Mass

Alcoholic liver disease (ALD) has become a critical global public health issue worldwide. Tartary buckwheat extracts exhibit potential therapeutic effects against ALD due to its antioxidant and anti-inflammatory activities. However, in vivo pharmacokinetics and metabolite identification of tartary buckwheat extracts have not been clearly elucidated. Accordingly, the current manuscript aimed to investigate pharmacokinetics and to identify novel metabolites in beagle dogs following oral co-administration of tartary buckwheat extracts and ethanol. To support pharmacokinetic study, a simple LC-MS/MS method was developed and validated for simultaneous determination of quercetin and kaempferol in beagle dog plasma. The conjugated forms of both analytes were hydrolyzed by β-glucuronidase and sulfatase followed by liquid-liquid extraction using methyl tert-butyl ether. In addition, another effective approach was established using advanced ultrafast liquid chromatography coupled with a Q-Exactive hybrid quadrupole orbitrap high resolution mass spectrometer to identify the metabolites in beagle dog biological samples including urine, feces, and plasma. The pharmacokinetic study demonstrated that the absolute oral bioavailability for quercetin and kaempferol was determined to be 4.6% and 1.6%, respectively. Oral bioavailability of quercetin and kaempferol was limited in dogs probably due to poor absorption, significant first pass effect, and biliary elimination, etc. Using high resolution mass spectrometric analysis, a total of nine novel metabolites were identified for the first time and metabolic pathways included methylation, glucuronidation, and sulfation. In vivo pharmacokinetics and metabolite identification results provided preclinical support of co-administration of tartary buckwheat extracts and ethanol in humans.

Experimental Study of the Impact of Alisma plantago-aquatica Secretions on Pathogenic Bacteria

2014 ◽  
Vol 1 (3) ◽  
pp. 3-7
Author(s):  
O. Zhukorskyy ◽  
O. Hulay
Keyword(s):  
Pathogenic Bacteria ◽  
Initial Density ◽  
Biologically Active ◽  
Erysipelothrix Rhusiopathiae ◽  
Natural Focus ◽  
Test Species ◽  
Popula Tions ◽  
And Control ◽  
The Impact

Aim. To estimate the impact of in vivo secretions of water plantain (Alisma plantago-aquatica) on the popula- tions of pathogenic bacteria Erysipelothrix rhusiopathiae. Methods. The plants were isolated from their natural conditions, the roots were washed from the substrate residues and cultivated in laboratory conditions for 10 days to heal the damage. Then the water was changed; seven days later the selected samples were sterilized using fi lters with 0.2 μm pore diameter. The dilution of water plantain root diffusates in the experimental samples was 1:10–1:10,000. The initial density of E. rhusiopathiae bacteria populations was the same for both experimental and control samples. The estimation of the results was conducted 48 hours later. Results. When the dilution of root diffusates was 1:10, the density of erysipelothrixes in the experimental samples was 11.26 times higher than that of the control, on average, the dilution of 1:100 − 6.16 times higher, 1:1000 – 3.22 times higher, 1:10,000 – 1.81 times higher, respectively. Conclusions. The plants of A. plantago-aquatica species are capable of affecting the populations of E. rhusiopathiae pathogenic bacteria via the secretion of biologically active substances into the environment. The consequences of this interaction are positive for the abovementioned bacteria, which is demon- strated by the increase in the density of their populations in the experiment compared to the control. The intensity of the stimulating effect on the populations of E. rhusiopathiae in the root diffusates of A. plantago-aquatica is re- ciprocally dependent on the degree of their dilution. The investigated impact of water plantain on erysipelothrixes should be related to the topical type of biocenotic connections, the formation of which between the test species in the ecosystems might promote maintaining the potential of natural focus of rabies. Keywords: Alisma plantago-aquatica, in vivo secretions, Erysipelothrix rhusiopathiae, population density, topical type of connections.

Changes in the Population Density of Pathogenic Microorganisms in Response to the Allelopathic Effect of Thypha Latifolia

2014 ◽  
Vol 1 (1) ◽  
pp. 31-36 ◽  
Author(s):  
O. Zhukorskiy ◽  
O. Gulay ◽  
V. Gulay ◽  
N. Tkachuk
Keyword(s):  
Cell Density ◽  
Allelopathic Effect ◽  
Pathogenic Microorganisms ◽  
Sterile Water ◽  
Erysipelothrix Rhusiopathiae ◽  
Pathogenic Leptospira ◽  
Favorable Conditions ◽  
And Control ◽  
The Impact ◽  
Control Samples

Aim. To determine the response of the populations of Erysipelothrix rhusiopathiae and Leptospira interrogans pathogenic microorganisms to the impact of broadleaf cattail (Thypha latifolia) root diffusates. Methods. Aqueous solutions of T. latifolia root diffusates were sterilized by vacuum fi ltration through the fi lters with 0.2-micron pore diameter. The experimental samples contained cattail secretions, sterile water, and cultures of E. rhusiopathiae or L. interrogans. The same amount of sterile water, as in the experimental samples, was used for the purpose of control, and the same quantity of microbial cultures was added in it. After exposure, the density of cells in the experimental and control samples was determined. Results. Root diffusates of T. latifolia caused an increase in cell density in the populations of E. rhusiopathiae throughout the whole range of the studied dilutions (1:10–1:10000). In the populations of the 6 studied serological variants of L. interrogans spirochetes (pomona, grippotyphosa, copenhageni, kabura, tarassovi, canicola), the action of broadleaf cattail root diffusates caused the decrease in cell density. A stimulatory effect was marked in the experimental samples of the pollonica serological variant of leptospira. Conclusions. The populations of E. rhusiopathiae and L. interrogans pathogenic microorganisms respond to the allelopathic effect of Thypha latifolia by changing the cell density. The obtained results provide the background to assume that broadleaf cattail thickets create favorable conditions for the existence of E. rhusiopathiae pathogen bacteria. The reduced cell density of L. interrogans in the experimental samples compared to the control samples observed under the infl uence of T. latifolia root diffusates suggests that reservoirs with broadleaf cattail thickets are marked by the unfavorable conditions for the existence of pathogenic leptospira (except L. pollonica).

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