Serveur d'exploration Chloroquine

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Rapid determination of gefitinib and its main metabolite, O-desmethyl gefitinib in human plasma using liquid chromatography-tandem mass spectrometry

Identifieur interne : 000052 ( PascalFrancis/Curation ); précédent : 000051; suivant : 000053

Rapid 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 :

RBID : Pascal:11-0332687

Descripteurs français

English descriptors

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).
pA  
A01 01  1    @0 1570-0232
A03   1    @0 J. chromatogr., B
A05       @2 879
A06       @2 22
A08 01  1  ENG  @1 Rapid determination of gefitinib and its main metabolite, O-desmethyl gefitinib in human plasma using liquid chromatography-tandem mass spectrometry
A11 01  1    @1 WANG (Ling-Zhi)
A11 02  1    @1 YI-XIU LIM (Michelle)
A11 03  1    @1 CHIN (Tan-Min)
A11 04  1    @1 THUYA (Win-Lwin)
A11 05  1    @1 NYE (Pei-Ling)
A11 06  1    @1 WONG (Andrea)
A11 07  1    @1 CHAN (Sui-Yung)
A11 08  1    @1 GOH (Boon-Cher)
A11 09  1    @1 HO (Paul C.)
A14 01      @1 Cancer Science Institute of Singapore, National University of Singapore @3 SGP @Z 1 aut. @Z 3 aut. @Z 4 aut. @Z 5 aut. @Z 8 aut.
A14 02      @1 Department of Pharmacy, National University of Singapore @3 SGP @Z 2 aut. @Z 7 aut. @Z 9 aut.
A14 03      @1 Department of Haematology & Oncology, National University Health System @3 SGP @Z 3 aut. @Z 6 aut. @Z 8 aut.
A20       @1 2155-2161
A21       @1 2011
A23 01      @0 ENG
A43 01      @1 INIST @2 8577B @5 354000190464250200
A44       @0 0000 @1 © 2011 INIST-CNRS. All rights reserved.
A45       @0 18 ref.
A47 01  1    @0 11-0332687
A60       @1 P
A61       @0 A
A64 01  1    @0 Journal of chromatography. B
A66 01      @0 NLD
C01 01    ENG  @0 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).
C02 01  X    @0 002B02A02
C02 02  X    @0 002A02
C03 01  X  FRE  @0 Analyse quantitative @5 01
C03 01  X  ENG  @0 Quantitative analysis @5 01
C03 01  X  SPA  @0 Análisis cuantitativo @5 01
C03 02  X  FRE  @0 Détermination @5 02
C03 02  X  ENG  @0 Determination @5 02
C03 02  X  SPA  @0 Determinación @5 02
C03 03  X  FRE  @0 Géfitinib @2 FR @5 03
C03 03  X  ENG  @0 Gefitinib @2 FR @5 03
C03 03  X  SPA  @0 Gefitinib @2 FR @5 03
C03 04  X  FRE  @0 Métabolite @5 04
C03 04  X  ENG  @0 Metabolite @5 04
C03 04  X  SPA  @0 Metabolito @5 04
C03 05  X  FRE  @0 Homme @5 05
C03 05  X  ENG  @0 Human @5 05
C03 05  X  SPA  @0 Hombre @5 05
C03 06  X  FRE  @0 Liquide biologique @5 06
C03 06  X  ENG  @0 Biological fluid @5 06
C03 06  X  SPA  @0 Líquido biológico @5 06
C03 07  X  FRE  @0 Plasma sanguin @5 07
C03 07  X  ENG  @0 Blood plasma @5 07
C03 07  X  SPA  @0 Plasma sanguíneo @5 07
C03 08  X  FRE  @0 Chromatographie HPLC @5 08
C03 08  X  ENG  @0 HPLC chromatography @5 08
C03 08  X  SPA  @0 Cromatografía HPLC @5 08
C03 09  X  FRE  @0 Spectrométrie masse tandem @5 09
C03 09  X  ENG  @0 Mass spectrometry MS/MS @5 09
C03 09  X  SPA  @0 Espectrometría masa en tándem @5 09
C03 10  X  FRE  @0 Anticancéreux @5 23
C03 10  X  ENG  @0 Antineoplastic agent @5 23
C03 10  X  SPA  @0 Anticanceroso @5 23
C03 11  X  FRE  @0 LC MS MS @4 INC @5 86
C07 01  X  FRE  @0 Inhibiteur enzyme @5 37
C07 01  X  ENG  @0 Enzyme inhibitor @5 37
C07 01  X  SPA  @0 Inhibidor enzima @5 37
C07 02  X  FRE  @0 Dérivé de la quinazoline @2 FR @5 38
C07 02  X  ENG  @0 Quinazoline derivatives @2 FR @5 38
C07 03  X  FRE  @0 Protein-tyrosine kinase @2 FE @5 39
C07 03  X  ENG  @0 Protein-tyrosine kinase @2 FE @5 39
C07 03  X  SPA  @0 Protein-tyrosine kinase @2 FE @5 39
C07 04  X  FRE  @0 Transferases @2 FE
C07 04  X  ENG  @0 Transferases @2 FE
C07 04  X  SPA  @0 Transferases @2 FE
C07 05  X  FRE  @0 Enzyme @2 FE
C07 05  X  ENG  @0 Enzyme @2 FE
C07 05  X  SPA  @0 Enzima @2 FE
C07 06  X  FRE  @0 Inhibiteur de la tyrosine kinase @5 40
C07 06  X  ENG  @0 Tyrosine kinase inhibitor @5 40
C07 06  X  SPA  @0 Inhibidor tyrosine kinase @5 40
C07 07  X  FRE  @0 Anti-EGFR @4 INC @5 87
N21       @1 227

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Pascal:11-0332687

Le document en format XML

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<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>
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<s2>879</s2>
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<fA06>
<s2>22</s2>
</fA06>
<fA08 i1="01" i2="1" l="ENG">
<s1>Rapid determination of gefitinib and its main metabolite, O-desmethyl gefitinib in human plasma using liquid chromatography-tandem mass spectrometry</s1>
</fA08>
<fA11 i1="01" i2="1">
<s1>WANG (Ling-Zhi)</s1>
</fA11>
<fA11 i1="02" i2="1">
<s1>YI-XIU LIM (Michelle)</s1>
</fA11>
<fA11 i1="03" i2="1">
<s1>CHIN (Tan-Min)</s1>
</fA11>
<fA11 i1="04" i2="1">
<s1>THUYA (Win-Lwin)</s1>
</fA11>
<fA11 i1="05" i2="1">
<s1>NYE (Pei-Ling)</s1>
</fA11>
<fA11 i1="06" i2="1">
<s1>WONG (Andrea)</s1>
</fA11>
<fA11 i1="07" i2="1">
<s1>CHAN (Sui-Yung)</s1>
</fA11>
<fA11 i1="08" i2="1">
<s1>GOH (Boon-Cher)</s1>
</fA11>
<fA11 i1="09" i2="1">
<s1>HO (Paul C.)</s1>
</fA11>
<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>
</fA14>
<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>
</fA14>
<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>
</fA14>
<fA20>
<s1>2155-2161</s1>
</fA20>
<fA21>
<s1>2011</s1>
</fA21>
<fA23 i1="01">
<s0>ENG</s0>
</fA23>
<fA43 i1="01">
<s1>INIST</s1>
<s2>8577B</s2>
<s5>354000190464250200</s5>
</fA43>
<fA44>
<s0>0000</s0>
<s1>© 2011 INIST-CNRS. All rights reserved.</s1>
</fA44>
<fA45>
<s0>18 ref.</s0>
</fA45>
<fA47 i1="01" i2="1">
<s0>11-0332687</s0>
</fA47>
<fA60>
<s1>P</s1>
</fA60>
<fA61>
<s0>A</s0>
</fA61>
<fA64 i1="01" i2="1">
<s0>Journal of chromatography. B</s0>
</fA64>
<fA66 i1="01">
<s0>NLD</s0>
</fA66>
<fC01 i1="01" l="ENG">
<s0>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).</s0>
</fC01>
<fC02 i1="01" i2="X">
<s0>002B02A02</s0>
</fC02>
<fC02 i1="02" i2="X">
<s0>002A02</s0>
</fC02>
<fC03 i1="01" i2="X" l="FRE">
<s0>Analyse quantitative</s0>
<s5>01</s5>
</fC03>
<fC03 i1="01" i2="X" l="ENG">
<s0>Quantitative analysis</s0>
<s5>01</s5>
</fC03>
<fC03 i1="01" i2="X" l="SPA">
<s0>Análisis cuantitativo</s0>
<s5>01</s5>
</fC03>
<fC03 i1="02" i2="X" l="FRE">
<s0>Détermination</s0>
<s5>02</s5>
</fC03>
<fC03 i1="02" i2="X" l="ENG">
<s0>Determination</s0>
<s5>02</s5>
</fC03>
<fC03 i1="02" i2="X" l="SPA">
<s0>Determinación</s0>
<s5>02</s5>
</fC03>
<fC03 i1="03" i2="X" l="FRE">
<s0>Géfitinib</s0>
<s2>FR</s2>
<s5>03</s5>
</fC03>
<fC03 i1="03" i2="X" l="ENG">
<s0>Gefitinib</s0>
<s2>FR</s2>
<s5>03</s5>
</fC03>
<fC03 i1="03" i2="X" l="SPA">
<s0>Gefitinib</s0>
<s2>FR</s2>
<s5>03</s5>
</fC03>
<fC03 i1="04" i2="X" l="FRE">
<s0>Métabolite</s0>
<s5>04</s5>
</fC03>
<fC03 i1="04" i2="X" l="ENG">
<s0>Metabolite</s0>
<s5>04</s5>
</fC03>
<fC03 i1="04" i2="X" l="SPA">
<s0>Metabolito</s0>
<s5>04</s5>
</fC03>
<fC03 i1="05" i2="X" l="FRE">
<s0>Homme</s0>
<s5>05</s5>
</fC03>
<fC03 i1="05" i2="X" l="ENG">
<s0>Human</s0>
<s5>05</s5>
</fC03>
<fC03 i1="05" i2="X" l="SPA">
<s0>Hombre</s0>
<s5>05</s5>
</fC03>
<fC03 i1="06" i2="X" l="FRE">
<s0>Liquide biologique</s0>
<s5>06</s5>
</fC03>
<fC03 i1="06" i2="X" l="ENG">
<s0>Biological fluid</s0>
<s5>06</s5>
</fC03>
<fC03 i1="06" i2="X" l="SPA">
<s0>Líquido biológico</s0>
<s5>06</s5>
</fC03>
<fC03 i1="07" i2="X" l="FRE">
<s0>Plasma sanguin</s0>
<s5>07</s5>
</fC03>
<fC03 i1="07" i2="X" l="ENG">
<s0>Blood plasma</s0>
<s5>07</s5>
</fC03>
<fC03 i1="07" i2="X" l="SPA">
<s0>Plasma sanguíneo</s0>
<s5>07</s5>
</fC03>
<fC03 i1="08" i2="X" l="FRE">
<s0>Chromatographie HPLC</s0>
<s5>08</s5>
</fC03>
<fC03 i1="08" i2="X" l="ENG">
<s0>HPLC chromatography</s0>
<s5>08</s5>
</fC03>
<fC03 i1="08" i2="X" l="SPA">
<s0>Cromatografía HPLC</s0>
<s5>08</s5>
</fC03>
<fC03 i1="09" i2="X" l="FRE">
<s0>Spectrométrie masse tandem</s0>
<s5>09</s5>
</fC03>
<fC03 i1="09" i2="X" l="ENG">
<s0>Mass spectrometry MS/MS</s0>
<s5>09</s5>
</fC03>
<fC03 i1="09" i2="X" l="SPA">
<s0>Espectrometría masa en tándem</s0>
<s5>09</s5>
</fC03>
<fC03 i1="10" i2="X" l="FRE">
<s0>Anticancéreux</s0>
<s5>23</s5>
</fC03>
<fC03 i1="10" i2="X" l="ENG">
<s0>Antineoplastic agent</s0>
<s5>23</s5>
</fC03>
<fC03 i1="10" i2="X" l="SPA">
<s0>Anticanceroso</s0>
<s5>23</s5>
</fC03>
<fC03 i1="11" i2="X" l="FRE">
<s0>LC MS MS</s0>
<s4>INC</s4>
<s5>86</s5>
</fC03>
<fC07 i1="01" i2="X" l="FRE">
<s0>Inhibiteur enzyme</s0>
<s5>37</s5>
</fC07>
<fC07 i1="01" i2="X" l="ENG">
<s0>Enzyme inhibitor</s0>
<s5>37</s5>
</fC07>
<fC07 i1="01" i2="X" l="SPA">
<s0>Inhibidor enzima</s0>
<s5>37</s5>
</fC07>
<fC07 i1="02" i2="X" l="FRE">
<s0>Dérivé de la quinazoline</s0>
<s2>FR</s2>
<s5>38</s5>
</fC07>
<fC07 i1="02" i2="X" l="ENG">
<s0>Quinazoline derivatives</s0>
<s2>FR</s2>
<s5>38</s5>
</fC07>
<fC07 i1="03" i2="X" l="FRE">
<s0>Protein-tyrosine kinase</s0>
<s2>FE</s2>
<s5>39</s5>
</fC07>
<fC07 i1="03" i2="X" l="ENG">
<s0>Protein-tyrosine kinase</s0>
<s2>FE</s2>
<s5>39</s5>
</fC07>
<fC07 i1="03" i2="X" l="SPA">
<s0>Protein-tyrosine kinase</s0>
<s2>FE</s2>
<s5>39</s5>
</fC07>
<fC07 i1="04" i2="X" l="FRE">
<s0>Transferases</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="04" i2="X" l="ENG">
<s0>Transferases</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="04" i2="X" l="SPA">
<s0>Transferases</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="05" i2="X" l="FRE">
<s0>Enzyme</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="05" i2="X" l="ENG">
<s0>Enzyme</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="05" i2="X" l="SPA">
<s0>Enzima</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="06" i2="X" l="FRE">
<s0>Inhibiteur de la tyrosine kinase</s0>
<s5>40</s5>
</fC07>
<fC07 i1="06" i2="X" l="ENG">
<s0>Tyrosine kinase inhibitor</s0>
<s5>40</s5>
</fC07>
<fC07 i1="06" i2="X" l="SPA">
<s0>Inhibidor tyrosine kinase</s0>
<s5>40</s5>
</fC07>
<fC07 i1="07" i2="X" l="FRE">
<s0>Anti-EGFR</s0>
<s4>INC</s4>
<s5>87</s5>
</fC07>
<fN21>
<s1>227</s1>
</fN21>
</pA>
</standard>
</inist>
</record>

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