Stereoselective Metabolism of Bufuralol Racemate and Enantiomers in Human Liver Microsomes

A new HPLC method was developed using a chiral column to efficiently separate four 1-hydroxybufuralol (1-OH-BF) di-astereomers that are major metabolites of bufuralol (BF). Em-ploying this method, we examined diastereomer selectivity in the formation of 1-OH-BF from BF racemate or enantiomers in four individual samples of human liver microsomes. Three dif-ferent human liver microsomes showed a selectivity of 1R-OH 1S-OH for BF enantiomers, which was similar to that of recombinant CYP2D6 expressed in insect cell microsomes, whereas one human liver microsomal fraction yielded a selec-tivity of 1R-OH 1S-OH for BF enantiomers, which was similar to those of recombinant CYP2C19 expressed in insect cell microsomes. Recombinant CYP1A2 and CYP3A4 showed a selectivity similar to that of CYP2D6, but their BF 1-hydrox