Stereospecificity of enzymatic hydrogen transfer to loxoprofen, a non-steroidal antiinflammatory agent, in the rat.
The in vitro metabolic reduction of loxoprofen in rat liver cytosolic fractions was investigated using a capillary gas-chromatography and electron ionization mass spectrometry (GC/MS). The formation rates of the corresponding trans- and cis-alcohol metabolites in the presence of non-labeled NADH were 3.5-fold higher than those of 4-(R)-[4-deuterated]-NADH as a cofactor. The representative mass fragment ion (m/z 319) derived from the trimethylsilyl derivatives of the latter alcohol products exhibited the ascending shift, suggesting the pro-4R hydrogen of NADH was transferred to loxoprofen. On the other hand, such significant differences in the metabolic activities and mass fragment grams were not observed whenever non-labeled NADPH or 4-(S)-[deuterated]-NADPH were employed.
Product Development Laboratories, Sankyo Co., Ltd., Tokyo, Japan.
H
H
Naganuma
Y
Y
Kawahara
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism*; D001711:Biotransformation; D003600:Cytosol / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D006859:Hydrogen / Q000378:metabolism; D007553:Isotope Labeling; D008099:Liver / Q000378:metabolism; D008297:Male; D009249:NADP / Q000378:metabolism; D010666:Phenylpropionates / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D010666:Phenylpropionates; C040656:loxoprofen; D009249:NADP; D006859:Hydrogen