Quantification of drugs with antimicrobial activity by high performance liquid chromatography coupled to mass spectrometry (LC-MS/MS): application in studies of comparative pharmacokinetics. / QuantificaÃÃo de fÃrmacos com atividade antimicrobiana em plasma humano por cromatografia lÃquida de alta eficiÃncia acoplada à espectrometria de massa (LC-MS/MS): aplicaÃÃo em estudos de farmacocinÃtica comparada

AUTOR(ES)

DemÃtrius Fernandes do Nascimento

FONTE

IBICT - Instituto Brasileiro de Informação em Ciência e Tecnologia

DATA DE PUBLICAÇÃO

31/10/2011

RESUMO

Two robust, fast and sensitive methods for quantification of sulfamethoxazole (SMX), trimethoprim (TMP) and sulfadiazine (SDZ) in plasma using high performance liquid chromatography coupled to mass spectrometry (LC-MS/MS) was developed and validated. The methods involved liquid-liquid extraction with ethyl acetate using metoprolol and sulfamethoxazole as internal standards (PI). The chromatographic separations were performed using Genesis C18 column 100 x 2.1 mm, 4 microns (sulfadiazine) and Genesis C18 150 x 4.6 mm, 4 microns (SMX+TMP), with elution systems consisting of solutions of methanol/water (35/65, v/v) + 0.5% Formic Acid (sulfadiazine) and methanol/water (45/55, v/v) + 0.5% Formic Acid (SMX+TMP). Calibration curves were linear in the range from 0.05 to 25 mg/mL (sulfadiazine); 0.5 to 100 mg/mL (SMX) and 0.02 to 3.5 mg/mL (TMP). The recoveries corresponding to the analysis of quality controls were 66.8, 59 and 63.4% for sulfadiazine; 67.7, 63.3 and 74.4% for SMX; 74.5, 70.5 and 78.1% for TMP. The recovery values relating to internal standards sulfamethoxazole and metoprolol were 66.2% and 76.8% respectively. The validated bioanalytical methods included evaluation of precision and accuracy being the results within the required limits. The methods were successfully applied in studies of comparative bioavailability of formulations containing a combination of sulfamethoxazole-trimethoprim (suspension containing 40mg of SMX and TMP 8mg per milliliter) and formulations containing sulfadiazine (tablets 500 mg) in healthy volunteers of both sexes

ASSUNTO(S)

farmacologia clinica sulfametoxazol trimetoprima sulfadiazina farmacocinÃtica ensaio clÃnico equivalÃncia terapÃutica

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