Electromembrane extraction of some antiepileptic drugs from biological fluids and quantification by capillary electrophoresis

Abstract

The monitoring of therapeutic drugs involves measuring drug concentrations in biological fluids such as plasma, serum, or blood. This information is used to individualize dosage to maintain drug concentrations within a target range (therapeutic window). For this purpose, the use of cheap, reliable, and fast analytical methods is considered. Phenytoin and clobazam need therapeutic drug monitoring due to their narrow therapeutic window and a high degree of protein binding. In the case of these drugs, it is preferable to measure the free concentration of the drug. In this dissertation, we summarized recent advancements in analytical approaches used for the determination of free drug concentration and plasma protein binding as a review article. In the next section, the use of exhaled breath condensate sample as a biological sample to determine the phenytoin was investigated. Electromembrane extraction (EME) followed by the capillary electrophoresis-diode array detection (CE-DAD) method was utilized for this purpose. Furthermore, the mechanism of drug (phenytoin) extraction from plasma samples by developed EME-CE-DAD was studied. This study aimed to answer the question of what form of the drug (free or total) is extracted in the EME method. The results showed that the EME method only leads to the extraction of the free form of the drug. Finally, the extraction of clobazam from plasma samples using EME-CE-DAD was investigated. The results showed that due to the lack of ionization of clobazam in the pH range of 1.0 to 14.0, it is not possible to extract this drug using this extraction method. Finally, the extraction performance of EME under ultrasound waves for extraction of clonazepam from plasma was studied. Ultrasound waves accelerate mass transfer and therefore increase extraction efficiency and decrease extraction time.