Capillary electrophoresis method for plasmatic determination of imatinib mesylate in chronic myeloid leukemia patients

• Published in: Electrophoresis 2011-07, Vol.32 (14), p.1885-1892
• Main Authors: Ajimura, Tatiana O., Borges, Keyller B., Ferreira, Aline F., de Castro, Fabíola A., de Gaitani, Cristiane M.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antineoplastic Agents - blood; Antineoplastic Agents - therapeutic use; Benzamides; Chronic myeloid leukemia; Drug Monitoring - methods; Drug Stability; Electrophoresis, Capillary - methods; Female; Human plasma; Humans; Imatinib; Imatinib Mesylate; Least-Squares Analysis; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - blood; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy; Male; Middle Aged; Piperazines - blood; Piperazines - therapeutic use; Pyrimidines - blood; Pyrimidines - therapeutic use; Reproducibility of Results; Sensitivity and Specificity; Validation
• ISSN: 0173-0835; 1522-2683
• DOI: 10.1002/elps.201000642

Imatinib (IMAT) is a tyrosine kinase inhibitor that has been used for the treatment of chronic myeloid leukemia (CML). Despite the efficacy of IMAT therapy, some cases of treatment resistance have been described in CML. Developing a plasma method is important since there are several studies that provided a higher correlation between IMAT plasma concentration and response to treatment. Therefore, in this investigation we validated a method by CE as an alternative, new, simple and fast electrophoretic method for IMAT determination in human plasma. The analysis was performed using a fused silica capillary (50 μm id×46.5 cm total length, 38.0 cm effective length); 50 mmol/L sodium phosphate buffer, pH 2.5, as BGE; hydrodynamic injection time of 20 s (50 mbar); voltage of 30 kV; capillary temperature of 35°C and detection at 200 nm. Plasma samples pre‐treatment involved liquid–liquid extraction with methyl‐tert‐butyl ether as the extracting solvent. The method was linear from 0.125 to 5.00 μg/mL. The LOQ was 0.125 μg/mL. Mean absolute recovery of IMAT was 67%. The method showed to be precise and accurate with RSD and relative error values lower than 15%. Furthermore, the application of the method was performed in the analysis of plasma samples from CML patients undergoing treatment with IMAT.