Rapid determination of gefitinib and its main metabolite, O-desmethyl gefitinib in human plasma using liquid chromatography-tandem mass spectrometry
Identifieur interne : 001598 ( Main/Exploration ); précédent : 001597; suivant : 001599Rapid determination of gefitinib and its main metabolite, O-desmethyl gefitinib in human plasma using liquid chromatography-tandem mass spectrometry
Auteurs : Ling-Zhi Wang [Singapour] ; Michelle Yi-Xiu Lim [Singapour] ; Tan-Min Chin [Singapour] ; Win-Lwin Thuya [Singapour] ; Pei-Ling Nye [Singapour] ; Andrea Wong [Singapour] ; Sui-Yung Chan [Singapour] ; Boon-Cher Goh [Singapour] ; Paul C. Ho [Singapour]Source :
- Journal of chromatography. B [ 1570-0232 ] ; 2011.
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- topic : Analyse quantitative, Homme.
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Abstract
A novel, rapid and specific liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed and validated for the simultaneous quantification of gefitinib and its predominant metabolite, O-desmethyl gefitinib in human plasma. Chromatographic separation of analytes was achieved on an Alltima C18 analytical HPLC column (150mm x 2.1 mm, 5 μm) using an isocratic elution mode with a mobile phase comprised acetonitrile and 0.1% formic acid in water (30:70, v/v). The flow rate was 300 μL/min. The chromatographic run time was 3 min. The column effluents were detected by API 4000 triple quadrupole mass spectrometer using electrospray ionization (ESI) in positive mode. Linearity was demonstrated in the range of 5-1000 ng/mL for gefitinib and 5-500 ng/mL for O-desmethyl gefitinib. The intra- and inter-day precisions for gefitinib and O-desmethyl gefitinib were ≤10.8% and the accuracies ranged from 89.7 to 104.7% for gefitinib and 100.4 to 106.0% for O-desmethyl gefitinib. This method was used as a bioanalytical tool in a phase I clinical trial to investigate the possible effect of hydroxychloroquine on the pharmacokinetics of gefitinib. The results of this study enabled clinicians to ascertain the safety of the combination therapy of hydroxychloroquine and gefitinib in patients with advanced (Stage IIIB-IV) non-small cell lung cancer (NSCLC).
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Ho</name><affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Department of Pharmacy, National University of Singapore</s1><s3>SGP</s3><sZ>2 aut.</sZ><sZ>7 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>Singapour</country><orgName type="university">Université nationale de Singapour</orgName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">11-0332687</idno><date when="2011">2011</date><idno type="stanalyst">PASCAL 11-0332687 INIST</idno><idno type="RBID">Pascal:11-0332687</idno><idno type="wicri:Area/PascalFrancis/Corpus">000014</idno><idno type="wicri:Area/PascalFrancis/Curation">000052</idno><idno type="wicri:Area/PascalFrancis/Checkpoint">000013</idno><idno type="wicri:explorRef" wicri:stream="PascalFrancis" wicri:step="Checkpoint">000013</idno><idno type="wicri:doubleKey">1570-0232:2011:Wang L:rapid:determination:of</idno><idno type="wicri:Area/Main/Merge">001600</idno><idno type="wicri:Area/Main/Curation">001598</idno><idno type="wicri:Area/Main/Exploration">001598</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Rapid determination of gefitinib and its main metabolite, O-desmethyl gefitinib in human plasma using liquid chromatography-tandem mass spectrometry</title><author><name sortKey="Wang, Ling Zhi" sort="Wang, Ling Zhi" uniqKey="Wang L" first="Ling-Zhi" last="Wang">Ling-Zhi Wang</name><affiliation wicri:level="4"><inist:fA14 i1="01"><s1>Cancer Science Institute of Singapore, National University of Singapore</s1><s3>SGP</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Singapour</country><orgName type="university">Université nationale de Singapour</orgName></affiliation></author><author><name sortKey="Yi Xiu Lim, Michelle" sort="Yi Xiu Lim, Michelle" uniqKey="Yi Xiu Lim M" first="Michelle" last="Yi-Xiu Lim">Michelle Yi-Xiu Lim</name><affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Department of Pharmacy, National University of Singapore</s1><s3>SGP</s3><sZ>2 aut.</sZ><sZ>7 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>Singapour</country><orgName type="university">Université nationale de Singapour</orgName></affiliation></author><author><name sortKey="Chin, Tan Min" sort="Chin, Tan Min" uniqKey="Chin T" first="Tan-Min" last="Chin">Tan-Min Chin</name><affiliation wicri:level="4"><inist:fA14 i1="01"><s1>Cancer Science Institute of Singapore, National University of Singapore</s1><s3>SGP</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Singapour</country><orgName type="university">Université nationale de Singapour</orgName></affiliation><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Department of Haematology & Oncology, National University Health System</s1><s3>SGP</s3><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Singapour</country><wicri:noRegion>Department of Haematology & Oncology, National University Health System</wicri:noRegion></affiliation></author><author><name sortKey="Thuya, Win Lwin" sort="Thuya, Win Lwin" uniqKey="Thuya W" first="Win-Lwin" last="Thuya">Win-Lwin Thuya</name><affiliation wicri:level="4"><inist:fA14 i1="01"><s1>Cancer Science Institute of Singapore, National University of Singapore</s1><s3>SGP</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Singapour</country><orgName type="university">Université nationale de Singapour</orgName></affiliation></author><author><name sortKey="Nye, Pei Ling" sort="Nye, Pei Ling" uniqKey="Nye P" first="Pei-Ling" last="Nye">Pei-Ling Nye</name><affiliation wicri:level="4"><inist:fA14 i1="01"><s1>Cancer Science Institute of Singapore, National University of Singapore</s1><s3>SGP</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Singapour</country><orgName type="university">Université nationale de Singapour</orgName></affiliation></author><author><name sortKey="Wong, Andrea" sort="Wong, Andrea" uniqKey="Wong A" first="Andrea" last="Wong">Andrea Wong</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Department of Haematology & Oncology, National University Health System</s1><s3>SGP</s3><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Singapour</country><wicri:noRegion>Department of Haematology & Oncology, National University Health System</wicri:noRegion></affiliation></author><author><name sortKey="Chan, Sui Yung" sort="Chan, Sui Yung" uniqKey="Chan S" first="Sui-Yung" last="Chan">Sui-Yung Chan</name><affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Department of Pharmacy, National University of Singapore</s1><s3>SGP</s3><sZ>2 aut.</sZ><sZ>7 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>Singapour</country><orgName type="university">Université nationale de Singapour</orgName></affiliation></author><author><name sortKey="Goh, Boon Cher" sort="Goh, Boon Cher" uniqKey="Goh B" first="Boon-Cher" last="Goh">Boon-Cher Goh</name><affiliation wicri:level="4"><inist:fA14 i1="01"><s1>Cancer Science Institute of Singapore, National University of Singapore</s1><s3>SGP</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Singapour</country><orgName type="university">Université nationale de Singapour</orgName></affiliation><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Department of Haematology & Oncology, National University Health System</s1><s3>SGP</s3><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Singapour</country><wicri:noRegion>Department of Haematology & Oncology, National University Health System</wicri:noRegion></affiliation></author><author><name sortKey="Ho, Paul C" sort="Ho, Paul C" uniqKey="Ho P" first="Paul C." last="Ho">Paul C. Ho</name><affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Department of Pharmacy, National University of Singapore</s1><s3>SGP</s3><sZ>2 aut.</sZ><sZ>7 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>Singapour</country><orgName type="university">Université nationale de Singapour</orgName></affiliation></author></analytic><series><title level="j" type="main">Journal of chromatography. B</title><title level="j" type="abbreviated">J. chromatogr., B</title><idno type="ISSN">1570-0232</idno><imprint><date when="2011">2011</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Journal of chromatography. B</title><title level="j" type="abbreviated">J. chromatogr., B</title><idno type="ISSN">1570-0232</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antineoplastic agent</term><term>Biological fluid</term><term>Blood plasma</term><term>Determination</term><term>Gefitinib</term><term>HPLC chromatography</term><term>Human</term><term>Mass spectrometry MS/MS</term><term>Metabolite</term><term>Quantitative analysis</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Analyse quantitative</term><term>Détermination</term><term>Géfitinib</term><term>Métabolite</term><term>Homme</term><term>Liquide biologique</term><term>Plasma sanguin</term><term>Chromatographie HPLC</term><term>Spectrométrie masse tandem</term><term>Anticancéreux</term><term>LC MS MS</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Analyse quantitative</term><term>Homme</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">A novel, rapid and specific liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed and validated for the simultaneous quantification of gefitinib and its predominant metabolite, O-desmethyl gefitinib in human plasma. Chromatographic separation of analytes was achieved on an Alltima C18 analytical HPLC column (150mm x 2.1 mm, 5 μm) using an isocratic elution mode with a mobile phase comprised acetonitrile and 0.1% formic acid in water (30:70, v/v). The flow rate was 300 μL/min. The chromatographic run time was 3 min. The column effluents were detected by API 4000 triple quadrupole mass spectrometer using electrospray ionization (ESI) in positive mode. Linearity was demonstrated in the range of 5-1000 ng/mL for gefitinib and 5-500 ng/mL for O-desmethyl gefitinib. The intra- and inter-day precisions for gefitinib and O-desmethyl gefitinib were ≤10.8% and the accuracies ranged from 89.7 to 104.7% for gefitinib and 100.4 to 106.0% for O-desmethyl gefitinib. This method was used as a bioanalytical tool in a phase I clinical trial to investigate the possible effect of hydroxychloroquine on the pharmacokinetics of gefitinib. The results of this study enabled clinicians to ascertain the safety of the combination therapy of hydroxychloroquine and gefitinib in patients with advanced (Stage IIIB-IV) non-small cell lung cancer (NSCLC).</div></front></TEI><affiliations><list><country><li>Singapour</li></country><orgName><li>Université nationale de Singapour</li></orgName></list><tree><country name="Singapour"><noRegion><name sortKey="Wang, Ling Zhi" sort="Wang, Ling Zhi" uniqKey="Wang L" first="Ling-Zhi" last="Wang">Ling-Zhi Wang</name></noRegion><name sortKey="Chan, Sui Yung" sort="Chan, Sui Yung" uniqKey="Chan S" first="Sui-Yung" last="Chan">Sui-Yung Chan</name><name sortKey="Chin, Tan Min" sort="Chin, Tan Min" uniqKey="Chin T" first="Tan-Min" last="Chin">Tan-Min Chin</name><name sortKey="Chin, Tan Min" sort="Chin, Tan Min" uniqKey="Chin T" first="Tan-Min" last="Chin">Tan-Min Chin</name><name sortKey="Goh, Boon Cher" sort="Goh, Boon Cher" uniqKey="Goh B" first="Boon-Cher" last="Goh">Boon-Cher Goh</name><name sortKey="Goh, Boon Cher" sort="Goh, Boon Cher" uniqKey="Goh B" first="Boon-Cher" last="Goh">Boon-Cher Goh</name><name sortKey="Ho, Paul C" sort="Ho, Paul C" uniqKey="Ho P" first="Paul C." last="Ho">Paul C. Ho</name><name sortKey="Nye, Pei Ling" sort="Nye, Pei Ling" uniqKey="Nye P" first="Pei-Ling" last="Nye">Pei-Ling Nye</name><name sortKey="Thuya, Win Lwin" sort="Thuya, Win Lwin" uniqKey="Thuya W" first="Win-Lwin" last="Thuya">Win-Lwin Thuya</name><name sortKey="Wong, Andrea" sort="Wong, Andrea" uniqKey="Wong A" first="Andrea" last="Wong">Andrea Wong</name><name sortKey="Yi Xiu Lim, Michelle" sort="Yi Xiu Lim, Michelle" uniqKey="Yi Xiu Lim M" first="Michelle" last="Yi-Xiu Lim">Michelle Yi-Xiu Lim</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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