A novel mass spectrometry method for the absolute quantification of several cytochrome P450 and uridine 5′-diphospho-glucuronosyltransferase enzymes in the human liver

2020 ◽  
Vol 412 (8) ◽  
pp. 1729-1740
Author(s):  
Yayao Lv ◽  
Hanqing Zhang ◽  
Guibin Wang ◽  
Chaoshuang Xia ◽  
Fangyuan Gao ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Cytochrome P450 ◽  
Human Liver ◽  
Absolute Quantification ◽  
Spectrometry Method ◽  
Mass Spectrometry Method ◽  
The Absolute

Mass spectrometry-based absolute quantification of microsomal cytochrome P450 2D6 in human liver

PROTEOMICS ◽  
2009 ◽  
Vol 9 (9) ◽  
pp. 2313-2323 ◽  
Author(s):  
Elmar Langenfeld ◽  
Ulrich M. Zanger ◽  
Klaus Jung ◽  
Helmut E. Meyer ◽  
Katrin Marcus
Keyword(s):  
Mass Spectrometry ◽  
Cytochrome P450 ◽  
Human Liver ◽  
Absolute Quantification ◽  
Cytochrome P450 2D6 ◽  
Microsomal Cytochrome ◽  
Microsomal Cytochrome P450 ◽  
P450 2D6

Metabolic Characteristics of SM-1, a Novel PAC-1 Derivative, in Human Liver Microsomes

2021 ◽  
Vol 17 ◽  
Author(s):  
Ya Gong ◽  
Peiqi Wang ◽  
Jianming Li ◽  
Jinsong Ding
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Enzyme Kinetics ◽  
Human Liver ◽  
Liver Microsomes ◽  
Human Liver Microsomes ◽  
Spectrometry Method ◽  
Mass Spectrometry Method ◽  
Metabolic Characteristics ◽  
Kinetics Of

Background and Objectives: SM-1 is a new synthetic small molecule compound with antitumor activity. The metabolism of SM-1 is a key parameter that needs to be evaluated to provide further insight into drug safety and efficacy in the early phases of drug development. Methods and Results: In this study, the biotransformation process of SM-1 including the metabolic pathways and major metabolites was investigated based on a liquid chromatography-mass spectrometry method. Upon incubation of SM-1 with human liver microsomes, five metabolites were identified, namely dihydrodiol formation (R1), hydroxylation (R2, R3 and R5), and debenzylation (R4) of SM-1, with R1 and R4 being the major metabolites. The enzyme kinetic parameters of SM-1 were determined by a liquid chromatography tandem mass spectrometry method. The enzyme kinetics of SM-1 obeyed the Michaelis-Menten equation. The Vmax, Km, and CLint of SM-1 in HLMs were 14.5 nmol/mg protein/h, 6.32 μM, and 2.29 mL/mg protein/h, respectively. The chemical inhibition studies showed that CYP450 isoenzymes were responsible for SM-1 metabolism in HLMs and CYP3A4 was the major CYP450 isoenzyme involved in the metabolism of SM-1; these findings were confirmed by using the human recombinant CYP3A4. Conclusions : Through identification of the biotransformation pathways and enzyme kinetics of SM-1, the metabolic enzymes for SM-1 in HLMs are characterized.

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