Deep Eutectic Solvent Extraction for Liquid Chromatographic Analysis of Capecitabine and Related Metabolites in Human Plasma

Abstract

We applied the deep eutectic solvent (DES) extraction for analyzing capecitabine (Cape), 5’-deoxy-5-fluorocytidine (DFCR), 5’-deoxy-5-fluorouridine (DFUR), and 5-fluorouracil (5-FU) in human plasma with LC–UV method. In this method, the DES, which was prepared by mixing trioctylmethylammonium chloride and pentafluorophenol in a 1:2 molar ratio, was used as extraction solvent for target analytes in the sample solution. The target analytes extracted by DES was then injected into a reversed-phase LC–UV system and were detected with ultraviolet at 270 nm for 5-FU, DFCR, and DFUR, and at 240 nm for Cape. Under the optimized conditions, this extraction resulted in enrichment factors for Cape, DFCR, DFUR, and 5-FU, ranging from 1.4 to 5.6. The determination coefficients of the calibration curves were r² > 0.9952 in the range of 0.05–10 µg/mL. The limits of detection and quantification ranged from 1.9 to 4.4 and from 6.4 to 14.7 ng/mL, respectively. The relative standard deviations of the peak areas obtained during intra-day determinations were within 9.8 %. The proposed method was further validated by the analysis of spiked human plasma samples.