Identification of the diastereomers of pentobarbital N-glucosides excreted in human urine.
A study was undertaken to determine if humans excreted pentobarbital N-glucosides as urinary metabolites following oral administration of pentobarbital. (1'RS,5RS)-1-(beta-D-Glucopyranosyl)pentobarbital ((1'RS,5RS)-PTBG) was isolated from the urine of one subject. The two diastereomers, (1'RS,5R)-PTBG and (1'RS,5S)-PTBG were separated and found to be identical to synthetic standards when compared using HPLC retention times coupled with UV (with and without post-column ionization) and mass spectrometry (HPLC/MS). A HPLC method was developed for detecting and quantifying (1'RS,5R)-PTBG, (1'RS,5S)-PTBG and pentobarbital in urine. Following a single oral dose of sodium pentobarbital to male subjects (n = 6), 1.6-6.2% of the pentobarbital dose was excreted as (1'RS,5S)-PTBG over 60 hours. (1'RS,5R)-PTBG was also detected in one subject and accounted for 0.3% of the pentobarbital dose. Using a modified HPLC system, the four pentobarbital N-glucosides were resolved and analysis of a partially purified pentobarbital N-glucoside extract from one subject indicated that only (1'R,5R)-PTBG and (1'S,5S)-PTBG could be detected as urinary excretion products. These results indicate that the side chain chirality of pentobarbital may influence the observed enantioselectivity for the formation and/or urinary excretion of the pentobarbital N-glucosides.
Soine
W H
WH
Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Richmond 23298-0540.
Soine
P J
PJ
England
T M
TM
Graham
R M
RM
Capps
G
G
D000328:Adult; D006801:Humans; D008297:Male; D015394:Molecular Structure; D010424:Pentobarbital / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000652:urine; D015203:Reproducibility of Results; D013237:Stereoisomerism
C092276:1-(glucopyranosyl)pentobarbital; D010424:Pentobarbital