Capillary electrophoretic chiral determination of mirtazapine and its main metabolites in human urine after enzymatic hydrolysis.
Capillary electrophoresis and liquid-phase microextraction using porous polypropylene hollow fibers were employed for the enantioselective analyses of mirtazapine and its metabolites demethylmirtazapine and 8-hydroxymirtazapine in human urine. Before the extraction, urine samples (1.0 mL) were submitted to enzymatic hydrolysis at 37 degrees C for 16 h. Then, the enzyme was precipitated with trichloroacetic acid, the pH was adjusted to 8 with 0.5 mol/L phosphate buffer solution (pH 11) and 15% sodium chloride was further added. The analytes were transferred from the aqueous donor phase, through n-hexyl ether (organic solvent immobilized in the fiber), into 0.01 moL/L acetic acid solution (acceptor phase). The electrophoretic analyses were carried out in 50 mmol/L phosphate buffer solution (pH 2.5) containing 0.55% w/v carboxymethyl-beta-cyclodextrin. The method was linear over the concentration range of 62.5-2500 ng/mL for each mirtazapine and 8-hydroxymirtazapine enantiomer and 62.5-1250 ng/mL for each demethylmirtazapine enantiomer. The quantification limit was 62.5 ng/mL for all the enantiomers. Within-day and between-day assay precision and accuracy were lower than 15% for all the enantiomers. Finally, the method proved to be suitable for pharmacokinetic studies.
de Santana
Fernando José Malagueño
FJ
Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Avenida Café SN, Ribeirão Preto, São Paulo, Brazil.
Lanchote
Vera Lúcia
VL
Bonato
Pierina Sueli
PS
D019075:Electrophoresis, Capillary / Q000379:methods*; D006801:Humans; D006868:Hydrolysis; D008803:Mianserin / Q000031:analogs & derivatives* / Q000652:urine; D000078785:Mirtazapine; D013696:Temperature
D008803:Mianserin; D000078785:Mirtazapine; C415843:8-hydroxymirtazapine; C119256:demethylmirtazapine