Quantification of imatinib in human plasma by high-performance liquid chromatography-tandem mass spectrometry.
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.
Titier
Karine
K
Department of Clinical Pharmacology and Toxicology, Pellegrin Hospital and University Victor Segalen, 33076 Bordeaux, France. karine.titier@pharmaco.u-bordeaux2.fr
Picard
Stéphane
S
Ducint
Dominique
D
Teilhet
Emmanuelle
E
Moore
Nicholas
N
Berthaud
Patrice
P
Mahon
François-Xavier
FX
Molimard
Mathieu
M
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*
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate