title: Quantification of imatinib in human plasma by high-performance liquid chromatography-tandem mass spectrometry.
abstract: Imatinib, also known as Gleevec or Glivec, is a selective tyrosine kinase inhibitor currently used for the treatment of Philadelphia chromosome-positive chronic myeloid leukemia (CML) and for other malignant pathologies. We have developed a LC-MS-MS [corrected] method that could be used for imatinib therapeutic drug monitoring in plasma. After a liquid-liquid extraction, the imatinib and its deuterated internal standard were eluted on an XTerra RP18 column with a gradient of acetonitrile-ammonium formiate buffer 4 mmol/L, pH 3.2. Imatinib was detected by electrospray ionization mass spectrometry with multiple reaction-monitoring mode. The calibration curves were linear over the range 10-5000 ng/mL. The limit of quantification was set at 10 ng/mL. The bias was lower than 8%. Intra-day and inter-day precisions were lower than 8%. The extraction recovery was higher than 90%. This method is simple, adapted to routine application, and allows accurate therapeutic monitoring of imatinib. It can be used to evaluate patient adherence to daily oral therapy, drug-drug interactions, or pharmacokinetic/pharmacodynamic relationships.
authors.affiliation: Department of Clinical Pharmacology and Toxicology, Pellegrin Hospital and University Victor Segalen, 33076 Bordeaux, France. karine.titier@pharmaco.u-bordeaux2.fr
authors.forename: Karine
authors.initials: K
authors.lastname: Titier
authors.forename: Stéphane
authors.initials: S
authors.lastname: Picard
authors.forename: Dominique
authors.initials: D
authors.lastname: Ducint
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Teilhet
authors.forename: Nicholas
authors.initials: N
authors.lastname: Moore
authors.forename: Patrice
authors.initials: P
authors.lastname: Berthaud
authors.forename: François-Xavier
authors.initials: FX
authors.lastname: Mahon
authors.forename: Mathieu
authors.initials: M
authors.lastname: Molimard
mesh_terms: D000970:Antineoplastic Agents / Q000097:blood*; D001549:Benzamides; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D016903:Drug Monitoring; D004355:Drug Stability; D006801:Humans; D000068877:Imatinib Mesylate; D010879:Piperazines / Q000097:blood*; D011743:Pyrimidines / Q000097:blood*; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate