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Biomedical subjects

R M Thompson

Publications and source records attributed to R M Thompson.

49 records · Page 3Linked to original sources
PubMedDate not supplied

Characterization of glucuronide metabolites of carbamazepine in human urine by gas chromatography and mass spectrometry.

Glucuronide metabolites of carbamazepine (5 H-dibenz[b,f]azepine-5-carboxamide) were identified in human urine following chromatography on XAD-2 resin, permethylation, and combined gas chromatography and mass spectrometry with an SE-30 capillary column. Eight glucuronide metabolites, previously unidentified in man, were characterized as their permethylated derivatives. These included carbamazepine N-glucuronide (M+. 482), three isomers of dihydroxycarbamazepine O-glucuronide (M+. 542), three isomers of hydroxymethoxycarbamazepine O-glucuronide (M+. 542), and one isomer of hydroxycarbamazepine O-glucuronide (M+. 512). Other glucuronide metabolites, previously identified following enzymatic hydrolysis, were characterized as the unhydrolyzed, permethylated glucuronides, 10,11-dihydro-10,11-di--hydroxy carbamazepine O-glucuronide (M+. 544), and three isomers of monohydroxycarbamazepine O-glucuronide (M+. 512).

Biotransformation↗
PubMedDate not supplied

Isolation and identification of major metabolites of tixocortol pivalate in human urine.

The metabolism of tixocortol pivalate (PIVALONE), an anti-inflammatory steroid without systemic glucocorticoid effects, has been investigated in man. The analysis was conducted using urine samples collected from two volunteers who had received a 2-g oral dose of 14C-tixocortol pivalate as an oral suspension. Metabolites were purified and isolated from urine by normal phase HPLC, and structural identification was achieved by desorption chemical ionization/NH3 and electron impact/direct line introduction mass spectrometry. Unchanged tixocortol pivalate was not detected in urine; all metabolites were sulfo- and glucurono-conjugates. Metabolites were identified in the neutral steroid fraction obtained after hydrolysis of conjugates. Metabolic transformations in common with cortisol were reduction of the 3-keto, delta 4 system, reduction of the C-20 carbonyl group, oxidation of the C-11 alcohol, and cleavage of the side chain at C-17. Specific metabolic pathways involving the C-21 thiol ester function were transformations into methylthio, methylsulfinyl and methylsulfonyl derivatives, and a reductive cleavage of the C-21-S bond leading to 21-methyl structures. Since none of these metabolites had binding affinity for glucocorticoid receptors in vitro, fast and extensive transformation of tixocortol pivalate into inactive metabolites provides an explanation for the large dissociation between the topical and systemic activities of this drug.

Adult↗
PubMedDate not supplied

Characterization of mephenytoin metabolites in human urine by gas chromatography and mass spectrometry.

Metabolites of mephenytoin (5-ethyl-3-methyl-5-phenylhydantoin) were characterized in human urine following chromatography on XAD-2 resin, permethylation, and combined gas chromatography and mass spectrometry. Four glucuronide metabolites previously unidentified in man were characterized as their permethylated derivatives by chemical-ionization and electron-impact mass spectrometry. These metabolites included 5-ethyl-5-(hydroxyphenyl)-3-methylhydantoin O-glucuronide; 5-hydroxyethyl-3-methyl-5-phenyl-hydantoin O-glucuronide; 5-ethyl-5-(hydroxymethoxyphenyl)-3-methylhydantoin O-glucuronide; and a metabolite tentatively identified as 5-ethyl-5-phenylhydantoin N3-glucuronide in which both N-demethylation and glucuronide conjugation of the hydantoin ring have occurred. Mephenytoin, N-demethylmephenytoin, 5-ethyl-5-(hydroxyphenyl)-3-methylhydantoin, and 5-ethyl-5-(hydroxymethoxyphenyl)-3-methylhydantoin were characterized in extracts of enzymatically hydrolyzed urine.

Adult↗
PubMedDate not supplied

5,5-Bis(3-hydroxyphenyl)hydantoin, a minor metabolite of diphenylhydantoin (dilantin) in the rat and human.

5,5-Bis(4-hydroxyphenyl) hydantoin has been identified as a minor metabolite of diphenylhydantoin (DPH) in the rat and human. This metabolite was synthesized in the laboratory from 4,4'-dihydroxybenzophenone. Gas chromatographic and mass spectrometric comparison of the permethylated synthetic compound with the permethylated derivative of the metabolite obtained from biological sources showed that they were identical. The metabolite was excreted as a glucuronide and accounted for about 1% of the total hydroxylated metabolites of DPH in human urine and rat bile. When the synthetic standard was added to the recirculating perfusate of the isolated perfused rat liver, a monoglucuronide, a trihydroxy-DPH glucuronide, and a dihydroxymethoxy-DPH glucuronide were identified in the bile.

Animals↗