Development of a simultaneous quantification method of imatinib and sunitinib and their main metabolites and its application in patients with gastrointestinal stromal tumor

Biomed Chromatogr. 2023 Dec 28:e5804. doi: 10.1002/bmc.5804. Online ahead of print.ABSTRACTCorrelations between plasma concentrations of imatinib and sunitinib with efficacy and toxicity have been established. It is crucial to develop a sensitive and precise method for determining the plasma concentrations of imatinib and sunitinib, along with their active metabolites, to facilitate therapeutic drug monitoring and individualized therapy. Plasma samples were separated on an Agilent ZORBAX SB-C18 chromatographic column using gradient elution. Quantification was performed using a mass spectrometer equipped with electrospray ionization in multiple reaction monitoring. The analysis time was 18 min per run, with all analytes and internal standards eluting within 8 min. The calibration range was 25-4000 ng/mL for imatinib, 5-800 ng/mL for N-desmethyl imatinib (CGP74588), and 2.5-400 ng/mL for sunitinib and N-desethyl sunitinib (SU12662). Intra- and inter-assay precision were both below 15%, and accuracy ranged between 90.0% and 101.9%. The method was successfully applied to determine blood samples from 120 patients with gastrointestinal stromal tumors who received imatinib (n = 115) and sunitinib (n = 5). It has been validated as linear, accurate, precise, and robust, making it suitable for therapeutic drug monitoring of imatinib and sunitinib in routine clinical practice.PMID:38152034 | DOI:10.1002/bmc.5804
Source: Biomedical Chromatography : BMC - Category: Biomedical Science Authors: Source Type: research