Development and validation of a new analytical method based on syringe-to-syringe reversed phase liquid-liquid microextraction followed by HPLC-MS/MS for determination of sunitinib in human biological fluids: A proposed method for therapeutic drug monitoring in renal cell carcinoma patients

Sunitinib is a multi-targeted tyrosine kinase inhibitor approved for the treatment of advanced renal cell cancer and imatinib-resistant gastrointestinal stromal tumors. The quantification of sunitinib concentration in human biological fluids is crucial due to its narrow therapeutic index. In the present research, a syringe-to-syringe reversed phase liquid-liquid microextraction method based on the in-situ decomposition of a deep eutectic solvent has been developed for the extraction of sunitinib from patient's biological samples. In the proposed method, briefly, sample solution was added into a syringe containing tetrabutylammonium bromide: octanol deep eutectic solvent. This caused the solvent to decompose, enabling the analyte to be extracted into the fine droplets of octanol that were subsequently collected in the narrow bore section of the syringe by pushing the syringe piston. The collected phase was then analyzed using high performance liquid chromatography-tandem mass spectrometry. Key parameters, including type and volume of deep eutectic solvent, pH of the sample solution, and ionic strength were optimized. Subsequently, the optimized method was validated, demonstrating acceptable limits of detection (0.65 and 0.68 ng mL- 1 in urine and plasma samples, respectively) and quantification (2.18 and 2.26 ng mL- 1 in urine and plasma samples, respectively). The method also exhibited broad linear ranges (2.18-500 and 2.26-500 ng mL- 1 in urine and plasma samples, respectively), good precision (relative standard deviation <= 5.3 %), and high absolute extraction recoveries (71 and 69 % in urine and plasma samples, respectively). The proposed method was successfully employed for the determination of sunitinib in plasma and urine samples of patients undergoing treatment for renal cell carcinoma.