Evaluation of microextractions techniques and nonaqueous capillary electrophoresis (NACE) for the determination of antidepressants in plasma samples for therapeutic drug monitoring

Author(s)

Ana Paula Formenton Catai

• Document type: Doctoral Thesis
• Press: Ribeirão Preto.
• Institution: Universidade de São Paulo (USP). Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (PCARP/BC)
• Defense date: 2012-03-02

Examining board members

Maria Eugenia Queiroz Nassur; Nilson Antonio de Assunção; Emanuel Carrilho; Cristiane Masetto de Gaitani

• Advisor: Maria Eugenia Queiroz Nassur

Abstract

Therapeutic monitoring allows individualization of the dose regimen and has been indicated for the monitoring of well-established therapeutic intervals. In psychiatric disorders, most of the patients require that the plasmatic concentrations to be within a fixed range, so the disorders are kept under control and the adverse effects are acceptable. The aim of the therapeutic monitoring is ensure clinical effectiveness and minimization of adverse effects of drugs prescribed at the clinic. New trends in analytical chemistry have been directed towards simplification and miniaturization of analytical systems, and minimization of organic solvents and sample volume. In this work, analytical methodologies using microextraction techniques, such as stir bar sorptive extraction (SBSE) and microextraction by packed sorbent (MEPS), in conjunction with capillary electrophoresis in a nonaqueous background electrolyte (NACE) were developed for therapeutic drug monitoring of selective serotonin reuptake inhibitors (SSRIs: fluoxetine, sertraline, paroxetine and citalopram) in plasma sample of patients in therapy with SSRIs. First, the optimization of electrophoretic separation of the SSRIs was carried out to obtain simultaneous analysis of all antidepressants. Among the conditions evaluated (different background electrolytes in aqueous and nonaqueous medium, micellar electrokinetic capillary chromatography, and NACE), NACE-UV gave the best results. In the sequence, the optimization of the inherent variables of microextraction techniques (SBSE and MEPS)aiming analyses time minimization and increase of analytical sensibilitywas carried out. For SBSE/NACE methodology development the variables such as time of extraction, temperature of extraction, and matrix pH were optimized. For MEPS/NACE methodology the variables matrix pH and the volume of draw-eject cycles were optimized. Analytical validation was carried out in agreement with the norms of National Health Surveillance Agency (ANVISA) for both of the proposed methods, in different plasmatic concentrations, which completed the therapeutic interval. The developed methods (SBSE/NACE e MEPS/NACE) were compared to the reference method, using liquid-liquid extraction (LLE/NACE). Microextraction techniques, compared to LLE, gave the following advantages: reutilization of the extraction phase, fewer numbers of steps for extraction, reduction of sample volume, and less consumption of organic solvents. According to the evaluated validation parameters, the standardized methods SBSE/NACE and MEPS/NACE can be used in the analyses of antidepressants (SSRIs) in plasma sample for therapeutic drug monitoring purposes. (AU)