Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.jchromb.2011.05.056
Title: Rapid determination of gefitinib and its main metabolite, O-desmethyl gefitinib in human plasma using liquid chromatography-tandem mass spectrometry
Authors: Wang, L.-Z. 
Lim, M.Y.-X.
Chin, T.-M. 
Thuya, W.-L. 
Nye, P.-L.
Wong, A.
Chan, S.-Y. 
Goh, B.-C.
Ho, P.C. 
Keywords: Gefitinib
Human plasma
LC-MS/MS
O-Desmethyl gefitinib
Issue Date: 15-Jul-2011
Citation: Wang, L.-Z., Lim, M.Y.-X., Chin, T.-M., Thuya, W.-L., Nye, P.-L., Wong, A., Chan, S.-Y., Goh, B.-C., Ho, P.C. (2011-07-15). Rapid determination of gefitinib and its main metabolite, O-desmethyl gefitinib in human plasma using liquid chromatography-tandem mass spectrometry. Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences 879 (22) : 2155-2161. ScholarBank@NUS Repository. https://doi.org/10.1016/j.jchromb.2011.05.056
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). © 2011 Elsevier B.V.
Source Title: Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
URI: http://scholarbank.nus.edu.sg/handle/10635/110776
ISSN: 15700232
DOI: 10.1016/j.jchromb.2011.05.056
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