Quantification of imatinib in human plasma by high-performance liquid chromatography-tandem mass spectrometry
Karine Titier1, Stéphane Picard, Dominique Ducint
1Department of Clinical Pharmacology and Toxicology, Pellegrin Hospital and University Victor Segalen, 33076 Bordeaux, France. karine.titier@pharmaco.u-bordeaux2.fr
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.
Insights
A new LC-MS-MS method accurately measures imatinib (Gleevec) in plasma for therapeutic drug monitoring. This simple technique aids in evaluating patient adherence and drug interactions in chronic myeloid leukemia (CML) treatment.
Area of Science:
- Pharmacology
- Analytical Chemistry
- Oncology
Background:
- Imatinib (Gleevec/Glivec) is a crucial tyrosine kinase inhibitor for Philadelphia chromosome-positive chronic myeloid leukemia (CML).
- Effective therapeutic drug monitoring (TDM) is essential for optimizing imatinib treatment outcomes.
- Existing methods may lack the simplicity or accuracy required for routine clinical application.
Purpose of the Study:
- To develop and validate a reliable liquid chromatography-tandem mass spectrometry (LC-MS-MS) method for imatinib quantification in human plasma.
- To establish a method suitable for routine therapeutic drug monitoring (TDM) of imatinib.
Main Methods:
- Liquid-liquid extraction of imatinib and a deuterated internal standard from plasma.
- Separation using an XTerra RP18 column with a gradient elution system.
- Detection via electrospray ionization mass spectrometry (ESI-MS) in multiple reaction monitoring (MRM) mode.
Main Results:
- Linear calibration curves were observed from 10-5000 ng/mL.
- The limit of quantification was 10 ng/mL, with bias <8% and precision <8% (intra- and inter-day).
- Extraction recovery exceeded 90%, indicating high efficiency.
Conclusions:
- The developed LC-MS-MS method is simple, accurate, and suitable for routine therapeutic drug monitoring of imatinib.
- This method facilitates the assessment of patient adherence, drug-drug interactions, and pharmacokinetic/pharmacodynamic relationships.
- Accurate imatinib monitoring can improve treatment efficacy and patient management in CML and other malignancies.
