Selective Method for Determination and Microextraction of Imatinib at Trace Levels: A Possible Dose Monitoring Technique in Cancer Patients

Background: Imatinib (Gleevec) is an antineoplastic agent acting as tyrosine kinase inhibitor used for the treatment of cancer such as lymphoblastic leukemia. The dosage of the anticancer drugs plays a critical role in the survival of the patients. Therefore, each patient should be administered with a customized dosage of the antineoplastic agent. For this reason, patients' plasma and urine samples should be monitored to obtain the necessary information regarding the toxicity of the drug. Objective: To determine the trace levels of imatinib, the trend solvent bar microextraction and hollow fiber liquid phase microextraction technique coupled with High-Performance Liquid Chromatography- Ultraviolet (HPLC-UV) detection were employed and optimized using Minitab. Method: In this method, pH gradient plays a critical role in obtaining the optimum results. Imatinib is a weak base so that the donor phase containing the drug was adjusted to 10.5 and the acceptor phase (free of drug) was adjusted to pH 2.8. N-octanol was used as the organic solvent to impregnate the pores of the hollow fiber so that the drug could enter the solvent bar. To enhance the results and shorten the time required, the other parameters such as stirring rate (750 rpm), time (20 min), temperature (25°C) and salt addition (14.2%) were optimized. Results: Under the optimum condition, the Limit Of Detection (LOD), Limit Of Quantification (LOQ), and Preconcentration Factor (PF) were obtained as 7.0 ng mL-1, 20.0 ng mL-1, and 107, respectively. The relative standard deviations of analysis were 4.9% within a day (n=3) and 5.7% between days (n=9). The calibration curves represented good linearity for urine and plasma samples with coefficient estimations higher than 0.99 with a linearity range of 20.0-6000.0 ng mL-1. Conclusion: Considering the results, it can be concluded that the present technique can be a great method in clinical applications, customized treatment and for clean validation in pharmaceutical industries.