Quantification of imatinib in human plasma by high-performance liquid chromatography-tandem mass spectrometry

Ther Drug Monit. 2005 Oct;27(5):634-40. doi: 10.1097/01.ftd.0000175973.71140.91.

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.

MeSH terms

  • Antineoplastic Agents / blood*
  • Benzamides
  • Chromatography, High Pressure Liquid / methods*
  • Drug Monitoring
  • Drug Stability
  • Humans
  • Imatinib Mesylate
  • Piperazines / blood*
  • Pyrimidines / blood*
  • Sensitivity and Specificity
  • Spectrometry, Mass, Electrospray Ionization / methods*

Substances

  • Antineoplastic Agents
  • Benzamides
  • Piperazines
  • Pyrimidines
  • Imatinib Mesylate