RESUMO
Topiramate (TPM) is the main antiepileptic drug used for the control of partial and generalized seizures in both adults and children. In association with clinical observations, the analysis of plasmatic concentration of TPM is of utmost importance for the individual adjustment of the administered dose to the patient. In the present work, a bioanalytical method was developed and validated for TPM analysis in plasma samples by capillary electrophoresis with capacitively-coupled contactless conductivity detection (CE-C4 D). A simple background electrolyte composed of 15 mmol/L triethylamine, hydrodynamic injections (0.8 psi for 5 s) and a moderate separation voltage (20 kV) were used, rendering relatively short analysis times (<3 min). The sample pre-treatment was carried out by liquid-liquid extraction using methyl terc-butyl ether as solvent and 200 µL of plasma. The method was validated according to the official guidelines from the European Medicine Agency and showed linearity in plasmatic concentration range from 1 to 30 µg/mL, which covers the clinically-relevant interval. The lower limit of quantification of 1 µg/mL obtained also allows following patients with low dosage of the drug. The method was successfully applied to analysis of plasma samples and allowed the identification of 80% under-medicated patients in the analyzed patient pool.
Assuntos
Anticonvulsivantes/sangue , Monitoramento de Medicamentos/métodos , Eletroforese Capilar/métodos , Topiramato/sangue , Anticonvulsivantes/uso terapêutico , Condutividade Elétrica , Epilepsia/tratamento farmacológico , Humanos , Limite de Detecção , Modelos Lineares , Reprodutibilidade dos Testes , Topiramato/uso terapêuticoRESUMO
Vitreous humor (VH) shows excellent potential as a matrix of choice for postmortem analytical toxicology due to the ease of sampling and low metabolic activity. This study demonstrates a simple and rapid analytical method to identify and quantify 3,4-methylenedioxyamphetamine, 3,4-methylenedioxymethamphetamine and 3,4-methylenedioxy-ethylamphetamine in VH. Samples were collected with a simple eye puncture procedure, followed by liquid-liquid extraction and derivatization with heptafluorobutyric anhydride and analysis via gas chromatography-mass spectrometry. The accuracy of the method ranged 97-103%, intra-assay precision was between 4.54 and 9.14% relative standard deviation (RSD) and interassay precision ranged from 6.92 to 10.59% RSD. Limits of detection and quantification ranged from 1.0 to 2.5 ng/mL and 10 ng/mL, respectively. The validated method was successfully applied to detect methylenedioxyamphetamine derivatives in VH samples collected from victims of fatal car crashes.