ISSN:
1573-904X
Keywords:
barbiturate
;
N-glycosylation
;
product enantioselectivity
;
pentobarbital
;
urinary excretion
;
phase II metabolism
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
Abstract A study was undertaken to determine if humans excreted pentobarbital N-glucosides as urinary metabolites following oral administration of pentobarbital. (l′RS,5RS)-l-β-D-Glucopyranosyl) pentobarbital ((l′RS,5RS)-PTBG) was isolated from the urine of one subject. The two diastereomers, (l′RS,5R)-PTBG and (l′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 (l′RS,5R)-PTBG, (l′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 (l′RS,5S)-PTBG over 60 hours. (l′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 (l′R,5R)-PTBG and (l′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.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1018989116505
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