Sensitive determination of methotrexate in plasma of children with acute leukemia using double-solvent supramolecular systemas a novel extractant for dispersive liquid-liquid microextraction

Abstract Methotrexate, as a folate antagonist, is one of the first anti-neoplasm drugs offered and is still used as an effective drug in the treatment of various malignancies.Methotrexate has a narrow treatment index and is associated with numerous side effects.In thisresearch, for the first time a double-solvent supramolecular system (DSS) was developed as an extractant without disperser solvent for dispersive liquid-liquid microextraction (DLLME). DSS−DLLME was applied to the extraction of methotrexate in plasma of children with acute leukemiaprior to itsdetermination by high-performance liquid chromatography–ultraviolet detection (HPLC−UV).In the present method, two long normal chain alcohols are mixed in a particular ratio, and then it is injected into the sample solution, which is on the magnetic stirrer. In this case, the mixture of the two alcohol changes to new supramolecular aggregate. This new supermolecule is used as an extractant, which has a higher extraction power than any of its components alone.Under the optimum conditions, the calibration graph was linear in the rage of 0.1–150 µg L−1 with detection limit of 0.03 µg L−1.Relative standard deviations (RSDs) including intra–day and inter–day of method based on7 replicate determinations of 100.0 µg L−1of methotrexate were 2.6% and 4.8%,respectively.The results proved that DSS−DLLME is a sensitive, very simple, inexpensive, environmental friendly, rapid and efficient method for the preconcentration of trace amount of drugs in biological samples.