LC determination of the diastereomers of 1-(beta-D-glucopyranosyl)phenobarbital in human urine

Abstract

The "product enantioselectivity" associated with the urinary excretion of the phenobarbital N-glucoside conjugates has not been determined previously. A liquid chromatography method using gradient elution was developed for quantifying both phenobarbital N-glucoside conjugates, phenobarbital, and p-hydroxyphenobarbital. Following a single oral dose of phenobarbital to male Caucasian and Oriental subjects, both phenobarbital N-glucoside conjugates were observed in the urine. In seven subjects, 3.3-10.6% of the phenobarbital dose was detected as a single phenobarbital N-glucoside (S configuration at the C-5 position of the barbiturate ring). The other phenobarbital N-glucoside diastereomer accounted for less than 1.5% of the phenobarbital dose. The urinary excretion of the major phenobarbital N-glucoside diastereomer paralleled the urinary excretion of phenobarbital and was comparable in both Caucasian and Oriental subjects. These results indicate a pronounced selectivity for the formation and/or urinary excretion of the phenobarbital N-glucosides.