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.

Gradient elution LC-MS determination of dasatinib in rat plasma and its pharmacokinetic study

“…In recent years, numerous laboratories have reported the use of high-throughput bioanalytical procedures for the quantification of antileukemia drugs [5,6], a small number of analytical methods have been reported for dasatinib based on high-performance thin-layer chromatography (HPTLC) or high-performance liquid chromatography (HPLC) or radioactive labeling methods [7][8][9] and a liquid chromatography-mass spectrometry (LC-MS) method for plasma determination of this agent [10][11][12][13]. As with most approaches used to quantify pharmaceuticals, analytical methods for measuring tyrosine kinase inhibitor levels have focused on each agent in isolation and generally have been applied to pharmaceutical analysis or plasma determination of the agent.…”

Pharmacokinetic/pharmacodynamic correlation and blood-level testing in imatinib therapy for chronic myeloid leukemia

“…The assays were based on rapid, simple and sensitive protocols that had been validated earlier. 35,36 There are other methods, such as HPLC coupled with UVdiode array detection, which can be used to quantify imatinib. However, these alternative assays must be validated to current guidelines stipulated by the FDA or another regulatory body, and ideally also cross validated against the already validated LC-MS/MS reference method.…”

Trough plasma imatinib levels are correlated with optimal cytogenetic responses at 6 months after treatment with standard dose of imatinib in newly diagnosed chronic myeloid leukemia

“…Plasma samples were precipitated and then analyzed using high performance liquid chromatography apparatus equipped with a mass spectrometric detector as previously described [13]. Molecular response was assessed every 3 months by means of the peripheral blood BCR-ABL/ABL ratio using RQ-PCR, as previously described [14].…”