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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
8
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pubmed:dateCreated |
1994-2-15
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pubmed:abstractText |
1. Potential sulphur-containing metabolites of the anticancer agent, fotemustine, were synthesized, namely thiodiacetic acid (TDA), S-2-hydroxyethyl N-acetyl-L-cysteine (2-HE-NAC), N-acetyl-L-cysteine (NAC), S-methyl N-acetyl-L-cysteine (M-NAC), S-carboxymethyl-L-cysteine (CM-Cys), S-carboxymethyl N-acetyl-L-cysteine (CM-NAC), their corresponding sulphoxides and sulphones. Their chemical structures and stabilities were confirmed and derivatization methods were developed for their analysis by sulphur-selective g.l.c. (g.l.c.-FPD) and g.l.c.-mass spectrometry. 2. Four methods for isolation of potential metabolites of fotemustine were developed. Quantification of metabolites, derived in various ways was carried out by g.l.c.-atomic emission detection (AED) or g.l.c.-mass spectrometry. 3. Male Wistar rats (n = 4) were given a single i.p. dose of 40 mg/kg fotemustine. Urine excretion of TDA (18.4 +/- 1.9% in 24 h) and TDA sulphoxide (12.0 +/- 1.6% in 24 h) was significant; 32.7 +/- 4.6% of the fotemustine dose was excreted as TDA, and TDA sulphoxide in 48 h. NAC was excreted in rat urine at 1% of the dose. No other potential glutathione-derived metabolites of fotemustine were excreted. 4. Male Wistar rats (n = 4) were also treated i.p. with fotemustine at 5, 20 and 40 mg/kg, to investigate dose dependency and the time course of excretion of TDA. Excretion of TDA in 48 h urine decreased from 32 +/- 2 to 17 +/- 2% dose (mean +/- SD) with increasing dose of fotemustine.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione,
http://linkedlifedata.com/resource/pubmed/chemical/Nitrosourea Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Organophosphorus Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Solvents,
http://linkedlifedata.com/resource/pubmed/chemical/fotemustine
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0049-8254
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
23
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
935-47
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:8284948-Animals,
pubmed-meshheading:8284948-Antineoplastic Agents,
pubmed-meshheading:8284948-Chromatography, Gas,
pubmed-meshheading:8284948-Freeze Drying,
pubmed-meshheading:8284948-Gas Chromatography-Mass Spectrometry,
pubmed-meshheading:8284948-Glutathione,
pubmed-meshheading:8284948-Male,
pubmed-meshheading:8284948-Molecular Structure,
pubmed-meshheading:8284948-Nitrosourea Compounds,
pubmed-meshheading:8284948-Organophosphorus Compounds,
pubmed-meshheading:8284948-Oxidation-Reduction,
pubmed-meshheading:8284948-Rats,
pubmed-meshheading:8284948-Rats, Wistar,
pubmed-meshheading:8284948-Solvents
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pubmed:year |
1993
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pubmed:articleTitle |
Identification and quantitative determination of glutathione-related urinary metabolites of fotemustine, a new anti-cancer agent.
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pubmed:affiliation |
Department of Pharmacochemistry, Free University, Amsterdam, The Netherlands.
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pubmed:publicationType |
Journal Article
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