Development and validation of an high performance liquid chromatography-tandem mass spectrometry method for the determination of imatinib 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 (R(2)=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.
Dipartimento di Chimica Generale ed Inorganica, Chimica Analitica, Chimica Fisica, Università degli Studi di Parma, Parco Area delle Scienze 17/A, 43124 Parma, Italy.
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Bianchi
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Caffarri
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Cavalli
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Lagrasta
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Musci
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Quaini
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Savi
D000818:Animals; D000970:Antineoplastic Agents / Q000032:analysis* / Q000493:pharmacokinetics; D001549:Benzamides / Q000032:analysis* / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D016903:Drug Monitoring / Q000379:methods*; D000068877:Imatinib Mesylate; D057230:Limit of Detection; D008099:Liver / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010879:Piperazines / Q000032:analysis* / Q000493:pharmacokinetics; D011743:Pyrimidines / Q000032:analysis* / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D012015:Reference Standards; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014018:Tissue Distribution
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate