Enantioselective Metabolism of Flufiprole in Rat and Human Liver Microsomes

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• 作者：Chunmian Lin ; Yelong Miao ; Mingrong Qian ; Qiang Wang ; Hu Zhang
• 刊名：Journal of Agricultural and Food Chemistry
• 出版年：2016
• 出版时间：March 23, 2016
• 年：2016
• 卷：64
• 期：11
• 页码：2371-2376
• 全文大小：312K
• ISSN：1520-5118

文摘

The enantioselective metabolism of flufiprole in rat and human liver microsomes in vitro was investigated in this study. The separation and determination were performed using a liquid chromatography system equipped with a triple-quadrupole mass spectrometer and a Lux Cellulose-2 chiral column. The enantioselective metabolism of rac-flufiprole was dramatically different in rat and human liver microsomes in the presence of the β-nicotinamide adenine dinucleotide phosphate regenerating system. The half-lives (t_1/2) of flufiprole in rat and human liver microsomes were 7.22 and 21.00 min, respectively, for R-(+)-flufiprole, whereas the values were 11.75 and 17.75 min, respectively, for S-(−)-flufiprole. In addition, the V_max of R-(+)-flufiprole was about 3-fold that of S-(−)-flufiprole in rat liver microsomes, whereas its value in the case of S-(−)-flufiprole was about 2-fold that of R-(+)-flufiprole in human liver microsomes. The CL_int of rac-flufiprole also showed opposite enantioselectivy in rat and human liver microsomes. The different compositions and contents of metabolizing enzyme in the two liver microsomes might be the reasons for the difference in the metabolic behavior of the two enantiomers.