Rapid biomonitoring of fluoropyrimidine-based chemotherapy drugs and their biometabolites in colorectal cancer patients' blood samples using an in-syringe-based fast drug extraction technique followed by LC-MS/MS analysis.

Patients with dihydropyrimidine dehydrogenase (DPD) deficiency in peripheral mononuclear cells are at higher risk of severe toxicity due to the improper dose of fluorouracil-based chemotherapy drugs, which has become an essential aspect for consideration in clinical studies. 5-fluorouracil (5-FU) is a first-line and second-line chemotherapy drug in adjuvant, neoadjuvant, or palliative therapy settings to treat solid tumors and cancers. In this work, a novel in-syringe-based fast drug extraction (IS-FaDEx) technique followed by UHPLC-MS/MS detection was developed for rapid biomonitoring of 5-FU and its biometabolites in human blood samples. In this process, the 5-FU drug and its metabolites were extracted using 1 mL of extraction solvent, and then, the cleanup was performed with solid sorbents under an semi-automated setup. Under optimized conditions, method validation results showed an excellent linearity range from 1∼1000 ng mL ^-1 with correlation coefficients >0.99. The detection limits varied between 0.4 and 2.0 ng mL ^-1 , recoveries of 5-FU and its biometabolites ranged from 94.9-107.5%, and relative standard deviation were between 3.1-8.3%. The overall analytical GREEnness (AGREE) score for the proposed method was determined to be 0.83 using the AGREE metric approach, showing an excellent greenness profile. Therefore, the developed method proved efficient, robust, semi-automated, and rapid, which can considerably minimize solvent, salts, and sorbent usage following green and sustainable chemistry principles. The current approach showed effectiveness in drug monitoring investigations and can be beneficial for enhancing the efficacy and safety of 5-FU-based chemotherapy in colorectal cancer patients.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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