title: Enantioselective Metabolism of Flufiprole in Rat and Human Liver Microsomes.
abstract: 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 (t1/2) 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 Vmax 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 CLint 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.
authors.affiliation: College of Biological and Environmental Engineering, Zhejiang University of Technology , Hangzhou 310014, China.
authors.forename: Chunmian
authors.initials: C
authors.lastname: Lin
authors.affiliation: College of Biological and Environmental Engineering, Zhejiang University of Technology , Hangzhou 310014, China.
authors.forename: Yelong
authors.initials: Y
authors.lastname: Miao
authors.affiliation: Institute of Quality and Standard for Agricultural Products, Zhejiang Academy of Agricultural Sciences , Hangzhou 310021, China.
authors.forename: Mingrong
authors.initials: M
authors.lastname: Qian
authors.affiliation: Institute of Quality and Standard for Agricultural Products, Zhejiang Academy of Agricultural Sciences , Hangzhou 310021, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Institute of Quality and Standard for Agricultural Products, Zhejiang Academy of Agricultural Sciences , Hangzhou 310021, China.
authors.forename: Hu
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D006207:Half-Life; D006801:Humans; D007306:Insecticides; D008862:Microsomes, Liver / Q000378:metabolism; D011720:Pyrazoles / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D053719:Tandem Mass Spectrometry
chemical_list: D007306:Insecticides; D011720:Pyrazoles; C000607325:1-(2,6-dichloro-4-trifluoromethylphenyl)-5-(N-(2-methylprop-2-enyl)amino)-4-trifluoromethylsulfinylpyrazole-3-carbonitrile
keywords: HPLC-MS/MS; enantioselective metabolism; flufiprole; liver microsomes