کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1221425 1494660 2013 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Development and validation of an high performance liquid chromatography–tandem mass spectrometry method for the determination of imatinib in rat tissues
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آنالیزی یا شیمی تجزیه
پیش نمایش صفحه اول مقاله
Development and validation of an high performance liquid chromatography–tandem mass spectrometry method for the determination of imatinib in rat tissues
چکیده انگلیسی

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 = 0.02 μg ml−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.


► 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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical and Biomedical Analysis - Volume 73, 25 January 2013, Pages 103–107
نویسندگان
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