Regioselective Differences in C8- and N-Oxidation of 2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline by Human and Rat Liver Microsomes and Cytochromes P450 1A2

2001 ◽  
Vol 14 (7) ◽  
pp. 901-911 ◽  
Author(s):  
Robert J. Turesky ◽  
Véronique Parisod ◽  
Tuong Huynh-Ba ◽  
Sophie Langouët ◽  
F. Peter Guengerich
Keyword(s):  
Rat Liver ◽  
Cytochromes P450 ◽  
Liver Microsomes ◽  
Rat Liver Microsomes

Differential roles of cytochromes P450 2D1, 2C11, and 1A1/2 in the hydroxylation of bufuralol by rat liver microsomes

1994 ◽  
Vol 47 (11) ◽  
pp. 1957-1963 ◽  
Author(s):  
Mayumi Mimura ◽  
Hiroshi Yamazaki ◽  
Chikako Sugahara ◽  
Toyoko Hiroi ◽  
Yoshihiko Funae ◽  
...  
Keyword(s):  
Rat Liver ◽  
Cytochromes P450 ◽  
Liver Microsomes ◽  
Rat Liver Microsomes

Cytochromes P450 Involved in Cyclophosphamide, Paclitaxel and Docetaxel Metabolism in Rats

2000 ◽  
Vol 65 (7) ◽  
pp. 1183-1190 ◽  
Author(s):  
Lucie Bořek-Dohalská ◽  
Ivan Gut ◽  
Pavel Souček ◽  
Zdeněk Roth ◽  
Petr Hodek
Keyword(s):  
Drug Metabolism ◽  
Anticancer Drugs ◽  
Rat Liver ◽  
Indirect Method ◽  
Cytochromes P450 ◽  
Liver Microsomes ◽  
Rat Liver Microsomes ◽  
Fast Estimation ◽  
Cyp Enzymes ◽  
Model Drug

We investigated involvement of cytochromes P450 (CYPs) of rat liver microsomes in metabolism of two anticancer drugs, paclitaxel (PCT) and docetaxel (DTX), by an indirect method. This method is based on the presumption that the compound competitively inhibiting oxidation of the CYP-selective substrate should also be a substrate for the CYP enzyme. The validity of this approach was confirmed using the model drug, cyclophosphamide (CPA). Indeed, CPA competitively inhibited oxidation of substrates specific for CYP2B1 and CYP3A1/2, enzymes previously reported to be capable of metabolizing CPA. Using this method, we identified CYP enzymes participating in PCT and DTX metabolism. The CYP2D1/2/3 and CYP3A1/2 are enzymes oxidizing PCT while CYP3A1/2 and CYP2E1 are responsible for metabolism of DTX. Here, we report a suitable method serving for easy and fast estimation of CYP enzymes involved in drug metabolism.

Metabolic Analysis of Triptolide Microspheres in Human, Dog, Rabbit and Rat Liver Microsomes with UPLC-MS/MS Method

2020 ◽  
Vol 17 ◽  
Author(s):  
LiJuan Wang ◽  
Yan Liu ◽  
Rui Li ◽  
DongXian He
Keyword(s):  
Rat Liver ◽  
Liver Microsomes ◽  
Internal Standard ◽  
Gradient Elution ◽  
Rat Liver Microsomes ◽  
Good Precision ◽  
Kinetics Parameters ◽  
Measure Concentration ◽  
Standard Curve ◽  
Variation Of Parameters

Objectives: Triptolide (TPL) has been shown to have a good clinical effect on rheumatoid arthritis (RA). We designed TPL microspheres (TPL-MS) and investigated its metabolic behavior in human, dog, rabbit and rat liver microsomes (HLM, DLM, RLM and SDRLM) with UPLC-MS/MS method. Methods: First, a UPLC-MS/MS method was established to measure concentration of TPL in samples. The sample was separated on a C18 column (2.1×100 mm, 1.8μm) and eluted with a gradient elution. The precursor ion/product ion were m/z 378.1/361.0 for TPL and 260.0/116.2 for the internal standard. Then T1/2, Vmax and CLint were calculated from the above data. Finally, the metabolites of TPL-MS were identified by high-resolution UPLC-MS/MS. The sample was separated on a C18 column (2.1×100 mm, 2.2 μm) and eluted with isocratic elution. Mass spectrometric detection was carried out on a thermo Q-exactive mass spectrometer with HESI. The scanning range of precursor ions was from m/z 50 to m/z 750. Result and Discussion: Through several indicators including standard curve, precision, accuracy, stability, matrix effect and recovery rate, the enzymatic kinetics parameters including T1/2, Vmax and CLint were completed. Several metabolites of TPL-MS were identified. Conclusion: UPLC-MS/MS method is an accurate and sensitive method for determination of TPL in liver microsome samples with good precision, accuracy and stability. The variation of parameters indicated that the microspheres can delay the elimination of TPL in liver microsomes. The metabolism of TPL-MS varied among species, but no new metabolites appeared.

scholarly journals The metabolism of gelsevirine in human, pig, goat and rat liver microsomes

2021 ◽  
Author(s):  
Hua‐Hai Zhang ◽  
Wen‐Jia Yang ◽  
Ya‐Jun Huang ◽  
Wen‐Jing Li ◽  
Shuo‐Xin Zhang ◽  
...  
Keyword(s):  
Rat Liver ◽  
Liver Microsomes ◽  
Rat Liver Microsomes
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