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).
View Article and Find Full Text PDFAmobarbital [5-ethyl-5-(3-methylbutyl)barbituric acid], USP, was found to contain an impurity that was not associated with hydrolysis and decomposition of the barbiturate ring. The impurity was isolated by semipreparative HPLC and was identified as 5-ethyl-5-(2-methylbutyl)barbituric acid (1) by MS (electron impact and chemical ionization) and 1H NMR. The substitution pattern on the alkyl side chain was verified by using the achiral NMR shift reagent tris(6,6,7,7,8,8,8-heptafluoro-2,2- dimethyl-3,5-octanedionato)europium(III).
View Article and Find Full Text PDFPreviously, the N-glucosylation of phenobarbital had been observed only in humans. The results of a species screen (mouse, rat, guinea pig, rabbit, cat, dog, pig, and monkey) found that only mice excreted the N-glucosides of phenobarbital in urine after ip administration of sodium phenobarbital. The major diastereomer excreted by the mouse had the R configuration at the C-5 position of the barbiturate ring.
View Article and Find Full Text PDFJ Pharm Biomed Anal
August 1992
A study was undertaken to determine if humans excreted barbital N-glucoside as a urinary metabolite following oral administration of barbital. A liquid chromatography method using gradient elution was developed for detecting and quantifying barbital N-glucoside and barbital in urine. Following a single oral dose of barbital to male caucasian and oriental subjects that had previously been shown to excrete amobarbital and phenobarbital N-glucosides, no barbital N-glucoside conjugate was observed in the urine.
View Article and Find Full Text PDFThe stereochemistry associated with the amobarbital N-glucoside diastereomers (1a and 1b) that are excreted by humans in urine is unknown. Using X-ray crystallography, the absolute configuration of 1b was determined to be S (C-5 position of the barbiturate ring). Following oral administration of amobarbital to Caucasians and Orientals, from 5 to 25% of the dose of amobarbital was excreted in the urine as 1b.
View Article and Find Full Text PDFThe absolute configuration of the N-beta-D-glucoside metabolites of phenobarbital was determined by methylation of the diastereomers to make mephobarbital N-beta-D-glucosides, followed by oxidative removal of glucose to give the optical isomers of mephobarbital. Following a single oral dose of phenobarbital to two male subjects, both phenobarbital N-beta-D-glucosides were excreted in the urine. The absolute configuration (C-5 position) of the major phenobarbital N-beta-D-glucoside excreted in the urine was the S form.
View Article and Find Full Text PDFJ Pharm Biomed Anal
August 1991
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.
View Article and Find Full Text PDFThe condensation of per(trimethyl)silylbarbital and -phenobarbital with 1,2,3,4,6-penta-O-acetyl-beta-D-glucopyranose in the presence of stannic chloride in dichloroethane gave moderate yields of the beta-coupled barbiturate N-D-glucopyranosyl derivatives. Reaction of metharbital and mephobarbital under the same conditions was unsuccessful. The homologous N-methylglucosides were prepared by reaction of the barbital and phenobarbital N-glucosyl derivatives with diazomethane.
View Article and Find Full Text PDFThe two diastereomers of 1-(1-beta-D-glucopyranosyl)phenobarbital, (1A) and (1B), decompose to 1-(1-beta-D-glucopyranosyl)-3-(2-ethyl-2-phenylmalonyl)urea (2A or 2B) followed by decarboxylation to 1-(1-beta-D-glucopyranosyl)-3-(2-phenylbutyryl)urea (3A and 3B) under physiological conditions of temperature and pH. The sigmoidal pH-rate profile and the Arrhenius parameters indicate that degradation takes place by hydroxide ion attack on the undissociated and monoanion forms of 1A and 1B. The rates of hydrolysis of the nonionized species of 1A and 1B are more than two orders of magnitude faster than those of common 5,5-disubstituted or 1,5,5-trisubstituted barbiturates.
View Article and Find Full Text PDFJ Toxicol Environ Health
December 1984
Chlordecone (CD) is an organochlorine pesticide associated with albumin and high-density lipoproteins (HDL) in the plasma. It is found in higher concentrations in the liver than in other tissues and is excreted in the bile. The influence of plasma HDL on the biliary excretion of CD was studied using isolated pig liver perfused with a Krebs-Ringer bicarbonate solution containing albumin, dextrose, and pig red blood cells.
View Article and Find Full Text PDFJ Toxicol Environ Health
December 1984
Cytosolic proteins may play an important role in the transport of water insoluble substances through the cytosol to various subcellular locations. The binding of chlordecone (CD) to pig liver cytosolic proteins was studied after the simultaneous administration of [14C]CD and [3H]cholesterol via the portal vein. The isolation of chlordecone binding proteins (CDBPs), from liver cytosol consisted of repeated ultracentrifugation, ammonium sulfate fractionation, and chromatography on Bio-Gel A 0.
View Article and Find Full Text PDFThe biotransformation of chlordecone (CD) to chlordecone alcohol (CDOH) occurs in man and gerbils but not in rats, guinea pigs and hamsters [1, 2]. Because of the species differences in CDOH formation and the need for a suitable animal model, pigs were administered CD by intraperitoneal (i.p.
View Article and Find Full Text PDFThe preferential distribution of the relatively nonpolar pesticide chlordecone (CD) to liver rather than to fat tissues in humans suggests that it may be transported in plasma differently from other organochlorine pesticides. The plasma binding of [14C] CD was investigated in vitro in human, rat, and pig plasma and in vivo in rat plasma. Protein and lipoprotein fractions were separated by serial ultracentrifugation.
View Article and Find Full Text PDFThe synthesis of the title compounds 1a and 1b has been accomplished in good yield by conversion of ketone 3 to the corresponding hydantoins 4a and 4b via a Bucherer-Bergs reaction, followed by barium hydroxide hydrolysis. The stereochemical assignments of the intermediate hydantoins 4a and 4b and the ethyl ester hydrochlorides 5a and 5b were determined by H NMR analysis. Attempts toward the synthesis of 2-amino-1,4-dihydro-1,4-ethanonaphthalene-2-carboxylic acid isomers 2a and 2b utilizing the pathway discussed for 1a and 1b led only to products arising from a retro-Diels-Alder reaction.
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