Identification and Characterization of a Novel Epoxide Hydrolase From Mouse Liver Microsomes

1982 ◽  
pp. 365-367 ◽  
Author(s):  
T. M. Guenthner ◽  
Ulla Vogel-Bindel ◽  
F. Oesch
Keyword(s):  
Mouse Liver ◽  
Epoxide Hydrolase ◽  
Liver Microsomes ◽  
Identification And Characterization

Identification and Characterization of Metabolites of Irinotecan in-vivo and in-vitro matrixes by HPLC/LC-MS

2016 ◽  
Vol 2 (3) ◽  
pp. 211-218
Author(s):  
Nidhi Srivastava ◽  
Vishal Dubey ◽  
Madhumita Sengar ◽  
Rastogi Sameer
Keyword(s):  
Method Development ◽  
Biological Fluids ◽  
Parent Compound ◽  
Enzymatic Reaction ◽  
Liver Microsomes ◽  
Metabolite Identification ◽  
Identification And Characterization

In the present study metabolite identification and characterization has done by using HPLC and LC-MS. During method development various mobile phases have tried for identification of metabolites. The matrixes selected for in- vivo study were urine because nearly all the metabolites of irinotecan were obtained in it. The extraction mixtures have selected to retain maximum amount of analyte with less effort. During experiment four extraction solvents were used in six different concentrations out of which TBME suit our method. In-vitro study done by Human Liver microsomes by using Phosphate buffer (pH 7.4) and NADPH as co-factors for initiation of enzymatic reaction. Irinotecan is a prodrug that is converted in the liver to an active metabolite, SN-38. It is eliminate in Bile and Faeces and thus its dose reduced in Hepatic Failure. Irinotecan act by inhibiting Topoisomerase-1.It is the enzyme which nicks, introduces negative supercoils and reseals the DNA strand. Conventionally, drug metabolite identification in the past has usually been based on the comparison of ultraviolet (UV) spectral data and high-performance liquid chromatography (HPLC) retention times of isolated ‘unknown’ metabolites with those of synthesised standards. Such a method of detecting and characterising drug metabolites is an uncertain, time-consuming and expensive process, as well as affording very limited structural information. Furthermore, Phase I metabolism of a drug candidate often results in only minor structural modification of the parent compound; these minor changes can make it particularly difficult to determine suitable chromatographic conditions to effect HPLC separation of metabolites. This study describes contemporary approach to identification and characterization of xenobiotic metabolites in complex biological fluids derived from drug metabolism studies.

Identification and Characterization of Oxymetazoline Glucuronidation in Human Liver Microsomes: Evidence for the Involvement of UGT1A9

2011 ◽  
Vol 100 (2) ◽  
pp. 784-793 ◽  
Author(s):  
Mukesh K. Mahajan ◽  
Vinita Uttamsingh ◽  
Liang-Shang Gan ◽  
Barbara Leduc ◽  
David A. Williams
Keyword(s):  
Human Liver ◽  
Liver Microsomes ◽  
Human Liver Microsomes ◽  
Identification And Characterization

Electrochemical Oxidation of Troglitazone: Identification and Characterization of the Major Reactive Metabolite in Liver Microsomes

2008 ◽  
Vol 21 (10) ◽  
pp. 2035-2041 ◽  
Author(s):  
Kim G. Madsen ◽  
Gunnar Grönberg ◽  
Christian Skonberg ◽  
Ulrik Jurva ◽  
Steen H. Hansen ◽  
...  
Keyword(s):  
Electrochemical Oxidation ◽  
Liver Microsomes ◽  
Reactive Metabolite ◽  
Identification And Characterization

scholarly journals Metabolic Stability and Metabolite Characterization of Capilliposide B and Capilliposide C by LC–QTRAP–MS/MS

Pharmaceutics ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 178 ◽  
Author(s):  
Zhongzhe Cheng ◽  
Xing Zhou ◽  
Zhifeng Du ◽  
Wenyi Li ◽  
Bingying Hu ◽  
...  
Keyword(s):  
Mouse Liver ◽  
Species Difference ◽  
Liver Microsomes ◽  
Metabolic Stability ◽  
Rat Liver Microsomes ◽  
Triterpenoid Saponins ◽  
Additional Information

Capilliposide B (LC-B) and Capilliposide C (LC-C), two new triterpenoid saponins extracted from Lysimachia capillipes Hemsl, exhibit potential anticancer activity both in vitro and in vivo. However, their metabolic process remains unclear. In this study, the metabolic stability of LC-B, LC-C, and Capilliposide A (LC-A, a bioactive metabolite of LC-B and LC-C) was investigated in human, rat, and mouse liver microsomes, respectively. Thereafter, their metabolites were identified and characterized after oral administration in mice. As a result, species difference was found in the metabolic stability of LC-B and LC-C. All three compounds of interest were stable in human and rat liver microsomes, but LC-B and LC-C significantly degraded in mouse liver microsomes. The metabolic instability of LC-B and LC-C was mainly caused by esterolysis. Moreover, 19 metabolites were identified and characterized in mouse biological matrices. LC-B and LC-C mainly underwent deglycosylation and esterolysis, accompanied by dehydration, dehydrogenation, and hydroxylation as minor metabolic reactions. Finally, the metabolic pathway of LC-B and LC-C in mice was proposed. Our results updated the preclinical metabolism and disposition process of LC-B and LC-C, which provided additional information for better understanding efficacy and safety.

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