Determination of 4-hydroxyifosfamide concomitantly with ifosfamide and its dechloroethylated metabolites using gas chromatography and a nitrogen phosphorus-selective detector
Identifieur interne : 000306 ( France/Analysis ); précédent : 000305; suivant : 000307Determination of 4-hydroxyifosfamide concomitantly with ifosfamide and its dechloroethylated metabolites using gas chromatography and a nitrogen phosphorus-selective detector
Auteurs : Bernard Gourmel [France] ; Camille P. Granvil [Canada] ; Sébastien L. Denis [France] ; Irving W. Wainer [Canada] ; Bernard Bousquet [France]Source :
- Journal of Chromatography B: Biomedical Sciences and Applications [ 0378-4347 ] ; 1999.
Abstract
A sensitive gas chromatographic (GC)/nitrogen phosphorus detection (NPD) system was developed for the determination of the antitumor drug ifosfamide (Ifos) and its 2-dechloroethylifosfamide (2-Difos), 3-dechloroethylifosfamide (3-Difos) and 4-hydroxyifosfamide (4-OHIfos) metabolites in human blood. 4-OHIfos was analyzed after coupling with a trapping agent and was used as an indicator of isophosphoramide mustard (IPM). Ifos and its metabolites 2-DIfos, 3-DIfos, 4-OHIfos and the internal standard (trofosfamide) were extracted into chloroform and then resolved by gas chromatography using a Hewlett Packard HP5 capillary column cross-linked with 5% phenyl methyl silicone (30 m; 530 μm I.D.; 2.65 μm film thickness). Precision and accuracy of the assay were determined over a three-day period and a concentration range of 3.25–50 μg/ml for Ifos, 0.8–14 μg/ml for 2D-Ifos, 0.6–10 μg/ml for 3D-Ifos and 0.08–1.40 μg/ml for 4-OHIfos. The limit of quantitation was set at 3.25, 0.80, 0.62 and 0.08 μg/ml, respectively, for Ifos, 2-DIfos, 3-DIfos and 4-OHIfos.The intra- and inter-day coefficients of variation and accuracies were less than 20%, except for a low concentration 4-OHIfos. This assay was then used to provide pharmacokinetic data on antitumor and toxicologic effects following intravenous infusion of Ifos.
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DOI: 10.1016/S0378-4347(99)00254-6
Affiliations:
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Wainer</name></author><author><name sortKey="Bousquet, Bernard" sort="Bousquet, Bernard" uniqKey="Bousquet B" first="Bernard" last="Bousquet">Bernard Bousquet</name></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:C3BBF230DE77E6FCD67D2583C3F068EC07A1A3E5</idno><date when="1999" year="1999">1999</date><idno type="doi">10.1016/S0378-4347(99)00254-6</idno><idno type="url">https://api-v5.istex.fr/document/C3BBF230DE77E6FCD67D2583C3F068EC07A1A3E5/fulltext/pdf</idno><idno type="wicri:Area/Istex/Corpus">001780</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">001780</idno><idno type="wicri:Area/Istex/Curation">001780</idno><idno type="wicri:Area/Istex/Checkpoint">001316</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Checkpoint">001316</idno><idno type="wicri:doubleKey">0378-4347:1999:Gourmel B:determination:of:hydroxyifosfamide</idno><idno type="wicri:Area/Main/Merge">003C56</idno><idno type="wicri:Area/Main/Curation">003677</idno><idno type="wicri:Area/Main/Exploration">003677</idno><idno type="wicri:Area/France/Extraction">000306</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a">Determination of 4-hydroxyifosfamide concomitantly with ifosfamide and its dechloroethylated metabolites using gas chromatography and a nitrogen phosphorus-selective detector</title><author><name sortKey="Gourmel, Bernard" sort="Gourmel, Bernard" uniqKey="Gourmel B" first="Bernard" last="Gourmel">Bernard Gourmel</name><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire de Biochimie, Hôpital Saint-Louis, Paris F-75010</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region></placeName></affiliation></author><author><name sortKey="Granvil, Camille P" sort="Granvil, Camille P" uniqKey="Granvil C" first="Camille P" last="Granvil">Camille P. Granvil</name><affiliation wicri:level="1"><country xml:lang="fr">Canada</country><wicri:regionArea>Département de Pharmacologie, Université de Montréal, Montreal, Quebec H3C 3J7</wicri:regionArea><wicri:noRegion>Quebec H3C 3J7</wicri:noRegion></affiliation></author><author><name sortKey="Denis, Sebastien L" sort="Denis, Sebastien L" uniqKey="Denis S" first="Sébastien L" last="Denis">Sébastien L. Denis</name><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire de Biochimie, Hôpital Saint-Louis, Paris F-75010</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region></placeName></affiliation></author><author><name sortKey="Wainer, Irving W" sort="Wainer, Irving W" uniqKey="Wainer I" first="Irving W" last="Wainer">Irving W. Wainer</name><affiliation wicri:level="4"><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Oncology, McGill University, Montreal, Quebec H3G 1A4</wicri:regionArea><orgName type="university">Université McGill</orgName><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author><author><name sortKey="Bousquet, Bernard" sort="Bousquet, Bernard" uniqKey="Bousquet B" first="Bernard" last="Bousquet">Bernard Bousquet</name><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire de Biochimie, Hôpital Saint-Louis, Paris F-75010</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region></placeName></affiliation></author></analytic><monogr></monogr><series><title level="j">Journal of Chromatography B: Biomedical Sciences and Applications</title><title level="j" type="abbrev">CHROLD</title><idno type="ISSN">0378-4347</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="1999">1999</date><biblScope unit="volume">732</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="3">3</biblScope><biblScope unit="page" to="15">15</biblScope></imprint><idno type="ISSN">0378-4347</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0378-4347</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">A sensitive gas chromatographic (GC)/nitrogen phosphorus detection (NPD) system was developed for the determination of the antitumor drug ifosfamide (Ifos) and its 2-dechloroethylifosfamide (2-Difos), 3-dechloroethylifosfamide (3-Difos) and 4-hydroxyifosfamide (4-OHIfos) metabolites in human blood. 4-OHIfos was analyzed after coupling with a trapping agent and was used as an indicator of isophosphoramide mustard (IPM). Ifos and its metabolites 2-DIfos, 3-DIfos, 4-OHIfos and the internal standard (trofosfamide) were extracted into chloroform and then resolved by gas chromatography using a Hewlett Packard HP5 capillary column cross-linked with 5% phenyl methyl silicone (30 m; 530 μm I.D.; 2.65 μm film thickness). Precision and accuracy of the assay were determined over a three-day period and a concentration range of 3.25–50 μg/ml for Ifos, 0.8–14 μg/ml for 2D-Ifos, 0.6–10 μg/ml for 3D-Ifos and 0.08–1.40 μg/ml for 4-OHIfos. The limit of quantitation was set at 3.25, 0.80, 0.62 and 0.08 μg/ml, respectively, for Ifos, 2-DIfos, 3-DIfos and 4-OHIfos.The intra- and inter-day coefficients of variation and accuracies were less than 20%, except for a low concentration 4-OHIfos. This assay was then used to provide pharmacokinetic data on antitumor and toxicologic effects following intravenous infusion of Ifos.</div></front></TEI><affiliations><list><country><li>Canada</li><li>France</li></country><region><li>Québec</li><li>Île-de-France</li></region><settlement><li>Montréal</li></settlement><orgName><li>Université McGill</li></orgName></list><tree><country name="France"><region name="Île-de-France"><name sortKey="Gourmel, Bernard" sort="Gourmel, Bernard" uniqKey="Gourmel B" first="Bernard" last="Gourmel">Bernard Gourmel</name></region><name sortKey="Bousquet, Bernard" sort="Bousquet, Bernard" uniqKey="Bousquet B" first="Bernard" last="Bousquet">Bernard Bousquet</name><name sortKey="Denis, Sebastien L" sort="Denis, Sebastien L" uniqKey="Denis S" first="Sébastien L" last="Denis">Sébastien L. Denis</name></country><country name="Canada"><noRegion><name sortKey="Granvil, Camille P" sort="Granvil, Camille P" uniqKey="Granvil C" first="Camille P" last="Granvil">Camille P. Granvil</name></noRegion><name sortKey="Wainer, Irving W" sort="Wainer, Irving W" uniqKey="Wainer I" first="Irving W" last="Wainer">Irving W. Wainer</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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