Evaluation of the ionic liquid based dispersive liquid-liquid microextraction technique to determination of levetiracetam by liquid chromatography mass-spectrometry

Abstract

Levetiracetam (LEV) is a new model of antiepileptic drug which has been effective in therapy for patients with treatment-refractory partial onset seizures with or without secondary generalization, both as adjunctive treatment and as monotherapy. The monitoring of plasmatic therapeutic concentration of drugs is more important in the treatment to epilepsy due the fact that epileptic patients generally require chronic therapy, often with two or more antiepileptic drugs at high doses. It is a challenge to determine drugs in complex matrices, like human plasma, due the multitude of endogenous compounds. In the last years, the interest for microextraction techniques in analytical chemistry field for the sample preparation has increased, highlighting the dispersive liquid-liquid microextraction (DLLME), due these techniques present some advantages in relation to other usual techniques, such as: simplicity of operation, rapidity, low quantity of sample and low use of organic solvents. In order to adapt different matrices and to achieve better extraction effects of hydrophilic drugs, as LEV, DLLME has been modified and been constantly improved. So, it was developed ionic liquids based dispersive liquid-liquid microextraction (IL-DLLME) because ILs show as an excellent choice to substitute the halogenated hydrocarbons, usually selected as extracting solvents of DLLME. Physical and chemical properties of ILs can be manipulated through judicious selection of the cation -anion combination and/or by introducing desired functional groups to either ionic moiety. However, ionic liquids are more expensive in Brazil, and functionalized ILs are not commercially available. In this context, this project aims to establish collaboration with the research group of prof. Dr. Wim Dehaen from KU Leuven in Belgium, who is expertise in synthesis of different ionic liquids. Thus, we propose to do a screening of a variety of ionic liquids and to test some as alternative of extracting solvent in DLLME and to obtain an adequate extraction of LEV in human plasma by liquid chromatography mass-spectroscopy (LC-MS/MS). (AU)