Determination of imatinib (Gleevec ®) in human plasma by solid-phase extraction–liquid chromatography–ultraviolet absorbance detection

A sensitive HPLC method has been developed for the assay of imatinib in human plasma, by off-line solid-phase extraction followed by HPLC coupled with UV-Diode Array Detection. Plasma (750 μl), with clozapine added as internal standard, is diluted 3+1 with water and subjected to a solid-phase extrac...

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Veröffentlicht in:Journal of chromatography. B, Analytical technologies in the biomedical and life sciences Analytical technologies in the biomedical and life sciences, 2004-04, Vol.803 (2), p.285-292
Hauptverfasser: Widmer, N, Béguin, A, Rochat, B, Buclin, T, Kovacsovics, T, Duchosal, M.A, Leyvraz, S, Rosselet, A, Biollaz, J, Decosterd, L.A
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container_issue 2
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container_title Journal of chromatography. B, Analytical technologies in the biomedical and life sciences
container_volume 803
creator Widmer, N
Béguin, A
Rochat, B
Buclin, T
Kovacsovics, T
Duchosal, M.A
Leyvraz, S
Rosselet, A
Biollaz, J
Decosterd, L.A
description A sensitive HPLC method has been developed for the assay of imatinib in human plasma, by off-line solid-phase extraction followed by HPLC coupled with UV-Diode Array Detection. Plasma (750 μl), with clozapine added as internal standard, is diluted 3+1 with water and subjected to a solid-phase extraction on a C18 cartridge. After matrix components elimination with 2000 μl of water (in two aliquots of 1000 μl), imatinib is eluted with 3×500 μl MeOH. The resulting eluate is evaporated under nitrogen at room temperature and is reconstituted in 180 μl 50% methanol. A 50 μl volume is injected onto a Nucleosil 100–5 μm C18 AB column. Imatinib is analyzed using a gradient elution program with solvent mixture constituted of methanol and water containing both 0.05% ammonium acetate. Imatinib is detected by UV at 261 nm. The calibration curves are linear between 0.1 and 10 μg/ml. The limit of quantification and detection are 0.05 and 0.01 μg/ml, respectively. The mean absolute recovery of imatinib is 96%. The method is precise with mean inter-day CVs within 1.1–2.4%, and accurate (range of inter-day deviations −0.6 to +0.7%). The method has been validated and is currently being applied in a clinical study assessing the imatinib plasma concentration variability in a population of chronic myeloid leukemia- and gastro-intestinal stromal tumor-patients.
doi_str_mv 10.1016/j.jchromb.2004.01.006
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B, Analytical technologies in the biomedical and life sciences</title><addtitle>J Chromatogr B Analyt Technol Biomed Life Sci</addtitle><description>A sensitive HPLC method has been developed for the assay of imatinib in human plasma, by off-line solid-phase extraction followed by HPLC coupled with UV-Diode Array Detection. Plasma (750 μl), with clozapine added as internal standard, is diluted 3+1 with water and subjected to a solid-phase extraction on a C18 cartridge. After matrix components elimination with 2000 μl of water (in two aliquots of 1000 μl), imatinib is eluted with 3×500 μl MeOH. The resulting eluate is evaporated under nitrogen at room temperature and is reconstituted in 180 μl 50% methanol. A 50 μl volume is injected onto a Nucleosil 100–5 μm C18 AB column. Imatinib is analyzed using a gradient elution program with solvent mixture constituted of methanol and water containing both 0.05% ammonium acetate. Imatinib is detected by UV at 261 nm. The calibration curves are linear between 0.1 and 10 μg/ml. The limit of quantification and detection are 0.05 and 0.01 μg/ml, respectively. The mean absolute recovery of imatinib is 96%. The method is precise with mean inter-day CVs within 1.1–2.4%, and accurate (range of inter-day deviations −0.6 to +0.7%). The method has been validated and is currently being applied in a clinical study assessing the imatinib plasma concentration variability in a population of chronic myeloid leukemia- and gastro-intestinal stromal tumor-patients.</description><subject>Analysis</subject><subject>Analytical, structural and metabolic biochemistry</subject><subject>Antineoplastic Agents - blood</subject><subject>Benzamides</subject><subject>Biological and medical sciences</subject><subject>Chromatography, High Pressure Liquid - methods</subject><subject>Fundamental and applied biological sciences. 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source MEDLINE; ScienceDirect Journals (5 years ago - present)
subjects Analysis
Analytical, structural and metabolic biochemistry
Antineoplastic Agents - blood
Benzamides
Biological and medical sciences
Chromatography, High Pressure Liquid - methods
Fundamental and applied biological sciences. Psychology
General pharmacology
Gleevec
Humans
Imatinib
Imatinib Mesylate
Medical sciences
Pharmacology. Drug treatments
Piperazines - blood
Pyrimidines - blood
Reproducibility of Results
Sensitivity and Specificity
Spectrophotometry, Ultraviolet - methods
title Determination of imatinib (Gleevec ®) in human plasma by solid-phase extraction–liquid chromatography–ultraviolet absorbance detection
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