title: Determination of imatinib (Gleevec) in human plasma by solid-phase extraction-liquid chromatography-ultraviolet absorbance detection.
abstract: 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 microl), 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 microl of water (in two aliquots of 1000 microl), imatinib is eluted with 3 x 500 microl MeOH. The resulting eluate is evaporated under nitrogen at room temperature and is reconstituted in 180 microl 50% methanol. A 50 microl volume is injected onto a Nucleosil 100-5 microm 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 microg/ml. The limit of quantification and detection are 0.05 and 0.01 microg/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.
authors.affiliation: Division de Pharmacologie Clinique, Laboratoire BH 18-218, Département de Médecine, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne CHUV, Switzerland.
authors.forename: N
authors.initials: N
authors.lastname: Widmer
authors.forename: A
authors.initials: A
authors.lastname: Béguin
authors.forename: B
authors.initials: B
authors.lastname: Rochat
authors.forename: T
authors.initials: T
authors.lastname: Buclin
authors.forename: T
authors.initials: T
authors.lastname: Kovacsovics
authors.forename: M A
authors.initials: MA
authors.lastname: Duchosal
authors.forename: S
authors.initials: S
authors.lastname: Leyvraz
authors.forename: A
authors.initials: A
authors.lastname: Rosselet
authors.forename: J
authors.initials: J
authors.lastname: Biollaz
authors.forename: L A
authors.initials: LA
authors.lastname: Decosterd
mesh_terms: D000970:Antineoplastic Agents / Q000097:blood*; D001549:Benzamides; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006801:Humans; D000068877:Imatinib Mesylate; D010879:Piperazines / Q000097:blood*; D011743:Pyrimidines / Q000097:blood*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013056:Spectrophotometry, Ultraviolet / Q000379:methods*
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate