ChloroquineV1, Main, Exploration, bibRecord, 001467

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

Identifieur interne : 001467 ( Main/Exploration ); précédent : 001466; suivant : 001468

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 ; Tan-Min Chin ; Win-Lwin Thuya ; Pei-Ling Nye ; Andrea Wong ; Sui-Yung Chan ; Boon-Cher Goh ; Paul C. Ho

Source :

Journal of chromatography. B, Analytical technologies in the biomedical and life sciences [ 1873-376X ] ; 2011.

RBID : pubmed:21703945

Descripteurs français

KwdFr :
- Antinéoplasiques (), Antinéoplasiques (pharmacocinétique), Antinéoplasiques (sang), Chromatographie en phase liquide (), Humains, Méthode des moindres carrés, Quinazolines (métabolisme), Quinazolines (pharmacocinétique), Quinazolines (sang), Reproductibilité des résultats, Spectrométrie de masse en tandem (), Stabilité de médicament.
MESH :
- métabolisme : Quinazolines.
- pharmacocinétique : Antinéoplasiques, Quinazolines.
- sang : Antinéoplasiques, Quinazolines.
- Antinéoplasiques, Chromatographie en phase liquide, Humains, Méthode des moindres carrés, Reproductibilité des résultats, Spectrométrie de masse en tandem, Stabilité de médicament.

English descriptors

KwdEn :
- Antineoplastic Agents (blood), Antineoplastic Agents (chemistry), Antineoplastic Agents (pharmacokinetics), Chromatography, Liquid (methods), Drug Stability, Gefitinib, Humans, Least-Squares Analysis, Quinazolines (blood), Quinazolines (metabolism), Quinazolines (pharmacokinetics), Reproducibility of Results, Tandem Mass Spectrometry (methods).
MESH :
- chemical , blood : Antineoplastic Agents, Quinazolines.
- chemical , chemistry : Antineoplastic Agents.
- chemical , metabolism : Quinazolines.
- chemical , pharmacokinetics : Antineoplastic Agents, Quinazolines.
- methods : Chromatography, Liquid, Tandem Mass Spectrometry.
- Drug Stability, Gefitinib, Humans, Least-Squares Analysis, Reproducibility of Results.

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 (150 mm × 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).

DOI: 10.1016/j.jchromb.2011.05.056
PubMed: 21703945

Affiliations:

Le document en format XML

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<term>Least-Squares Analysis</term>
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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 (150 mm × 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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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.

Source :

Descripteurs français

English descriptors

Abstract

Links toward previous steps (curation, corpus...)

Le document en format XML

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