Determinação simplificada de carbamazepina, fenitoína, fenobarbital e lamotrigina em plasma e monitoração terapêutica por HPLC/PDA

Carbamazepina, fenitoina, fenobarbital e lamotrigina sao bem conhecidos como farmacos anticonvulsivantes usados para o tratamento da epilepsia. A utilizacao destes farmacos e associada a varias reacoes adversas, tornando necessario o controle terapeutico. Os ensaios foram realizados por meio de cromatografia liquida de alta eficiencia e o metodo de extracao utilizado foi o liquido-liquido. Os farmacos e o padrao interno de zolpidem foram separados por uma coluna de fase reversa (ACE 5, C18 150 x 4,6 mm d.i.). A fase movel constituida de acetonitrila (30%) e acido citrico/tampao fosfato pH 5,0 (70%) foi utilizada sob gradiente de fluxo de 0,7 a 1,2 mL/min e o comprimento de onda utilizado para a deteccao dos analitos foi fixado em 210 nm. A tecnica apresentou linearidade ao longo do intervalo de 0,5 a 20,0 µg/mL para carbamazepina/lamotrigina e de 2,0 a 64,0 µg/mL, para fenitoina/ fenobarbital com coeficiente de correlacao linear maior que 0,98. As amostras de sangue foram obtidas de pacientes adultos com diagnostico de epilepsia em acompanhamento no Ambulatorio Municipal de Psiquiatria de Goiânia. A media de recuperacao obtida foi de 96,8% a 108,5% para carbamazepina/lamotrigina e de 93,8% a 108,8% para a fenitoina/fenobarbital. Os limites de quantificacao, precisao (CV 85,0 %) demonstraram estar em conformidade com as exigencias da ANVISA. Nove pacientes foram avaliados para confirmar a validade do metodo. Palavras-chave:Anticonvulsivantes. Monitoracao terapeutica de farmacos. HPLC. ABSTRACT Simplified determination of carbamazepine, phenytoin, phenobarbital and lamotrigine in plasma and therapeutic monitoring by HPLC/PDA Carbamazepine, phenytoin, phenobarbital and lamotrigine are well known anticonvulsant drugs used in the treatment of epilepsy. However, these medications are associated with side effects and therefore require therapeutic monitoring. Blood samples of adult outpatients diagnosed with epilepsy at the Goiânia Municipal Psychiatry Clinic (Brazil) were collected and analyzed using high-performance liquid chromatography. The analytes and internal standard (zolpidem) were extracted by liquid-liquid extraction. A reversed phase column (ACE 5, C18, 150 x 4.6 mm i.d.) was used. The mobile phase was composed of acetonitrile (30%) and citric acid/phosphate buffer, pH 5.0 (70%). The gradient flow rate was from 0.7 to 1.2 mL/min and the detection wavelength was set at 210 nm for all analytes. The analysis revealed a linear range from 0.5 to 20.0 µg/mL for carbamazepine/lamotrigine and 2.0 to 64.0 µg/mL for phenytoin/phenobarbital. Mean recovery ranged from 96.8% to 108.5% for carbamazepine/lamotrigine and 93.8% to 108.8% for phenytoin/phenobarbital. The quantification limit, precision (CV 85%) proved to be in accordance with the requirements stipulated by the Brazilian National Health Surveillance Agency (ANVISA). Nine outpatients were evaluated to confirm the validity of the method. Keywords: Anticonvulsant. Therapeutic drug monitoring. HPLC.