ChloroquineV1, PascalFrancis, Checkpoint, bibRecord, 000013

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

Identifieur interne : 000013 ( PascalFrancis/Checkpoint ); précédent : 000012; suivant : 000014

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 :

Journal of chromatography. B [ 1570-0232 ] ; 2011.

RBID : Pascal:11-0332687

Descripteurs français

Pascal (Inist)
- Analyse quantitative, Détermination, Géfitinib, Métabolite, Homme, Liquide biologique, Plasma sanguin, Chromatographie HPLC, Spectrométrie masse tandem, Anticancéreux, LC MS MS.
Wicri :
- topic : Analyse quantitative, Homme.

English descriptors

KwdEn :
- Antineoplastic agent, Biological fluid, Blood plasma, Determination, Gefitinib, HPLC chromatography, Human, Mass spectrometry MS/MS, Metabolite, Quantitative analysis.

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).

Affiliations:

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Pascal:11-0332687

Le document en format XML

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<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>
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<s5>01</s5>
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<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>
<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>

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

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

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