Development and validation of an high performance liquid chromatography–tandem mass spectrometry method for the determination of imatinib in rat tissues

• Published in: Journal of pharmaceutical and biomedical analysis Vol. 73; no. 25; pp. 103 - 107
• Main Authors: Bianchi, F., Caffarri, E., Cavalli, S., Lagrasta, C., Musci, M., Quaini, F., Savi, M.
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Amsterdam Elsevier B.V 25-01-2013; Elsevier
• Subjects: administered dose; Analysis; Analytical, structural and metabolic biochemistry; Animals; antineoplastic agents; Antineoplastic Agents - analysis; Antineoplastic Agents - pharmacokinetics; Benzamides - analysis; Benzamides - pharmacokinetics; Biological and medical sciences; Biological tissues; cardioprotective effect; Chromatography, High Pressure Liquid - methods; Drug Monitoring - methods; Fundamental and applied biological sciences. Psychology; gastrointestinal system; General pharmacology; heart; HPLC–MS/MS; Imatinib; Imatinib Mesylate; Limit of Detection; liquid chromatography; liver; Liver - metabolism; Male; Medical sciences; monitoring; myeloid leukemia; Myocardium - metabolism; Pharmacology. Drug treatments; Piperazines - analysis; Piperazines - pharmacokinetics; Pyrimidines - analysis; Pyrimidines - pharmacokinetics; Rats; Rats, Wistar; Reference Standards; Reproducibility of Results; Sample treatment; solvents; tandem mass spectrometry; Tandem Mass Spectrometry - methods; Tissue Distribution; tyrosine; Validation; Validation; Sample treatment; Imatinib; HPLC–MS/MS; Biological tissues; Antineoplastic agent; Rat; HPLC chromatography; Determination; Pyridine derivatives; Tissue; Alkaloid; Sample preparation; Development; Protein-tyrosine kinase; Quantitative analysis; Enzyme; Tyrosine kinase inhibitor; Transferases; Rodentia; Enzyme inhibitor; Vertebrata; Mammalia; HPLC-MS/MS; Animal; Benzamide derivatives; Pyrimidine derivatives; Piperazine derivatives
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/j.jpba.2012.05.034

► An HPLC–MS/MS method for imatinib determination in rat tissues was developed. ► Quantification limit, linearity, precision and recovery were evaluated. ► Rats were treated with imatinib and carvedilol, a cardioprotective drug. ► Amount of imatinib in rat tissues is dose-dependent. ► Carvedilol has no effect on imatinib concentrations in rat tissues.
An high performance liquid chromatography–tandem mass-spectrometry (HPLC–MS/MS) method was developed and validated for the determination in rat heart and liver of the tyrosine kinase inhibitor imatinib (IM), an anticancer drug approved for the treatment of chronic myeloid leukemia and gastrointestinal stromal tumors. Extraction of the drug from tissues was performed by solvent extraction and the obtained extracts were analyzed by HPLC–MS/MS in selected reaction monitoring mode. The developed method was validated according to the criteria for bioanalytical method, showing good performances in terms of lower limit of quantification (LLOQ=0.02μgml−1), linearity (R2=0.998), repeatability (RSD<3%), reproducibility (RSD<13%) and recovery (RR>89%). The developed method was then applied to the analysis of heart and liver of rats treated with different doses of IM, with and without the simultaneous administration of carvedilol, a beta-blocking agent with cardioprotective effect, in order to evaluate tissue levels of the tyrosine kinase inhibitor. The obtained results revealed that the amount of IM in the rat heart was significantly affected by the administered dose, whereas carvedilol had no effect on IM concentrations. Thus, we have developed a method that allows the detection of IM traces in complex tissues such as the heart and liver and that may be proposed for the determination of the drug in other clinically relevant biological samples.