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.