RESUMO
In this study, a simple method using microextraction by packed sorbent and high-performance liquid chromatography with ultraviolet detection for simultaneous determination of chlorpropamide, gliclazide and glimepiride in human plasma was developed and validated. A fractional factorial design and a complete factorial design were applied to evaluate the parameters which could affect the extraction and desorption steps, respectively. All parameters in the extraction step (pH, sample volume, sample dilution and number of aspiration/ejection cycles) and in the desorption step (percentage of acetonitrile in the elution solvent and number of aspirations of elution solvent through the device) were statistically significant (p>0.05) when recovery was used as response. The developed method allowed the use of small volumes of sample and solvents and rapid separation by using a fused core column (only 2.2min were needed). This method was fully validated showing selectivity, precision, accuracy and linearity over the range 1.0-50.0µgmL(-1) for chlorpropamide, 1.0-10.0µgmL(-1) for gliclazide and 0.1-1.0µgmL(-1) for glimepiride. Finally, the validated method was applied in the analysis of samples from volunteers containing the three tested analytes.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Hipoglicemiantes/sangue , Microextração em Fase Sólida/métodos , Clorpropamida/sangue , Gliclazida/sangue , Humanos , Concentração de Íons de Hidrogênio , Reprodutibilidade dos Testes , Compostos de Sulfonilureia/sangueRESUMO
OBJECTIVE: To compare the bioavailability of two glimepiride 4-mg tablet formulation in 26 healthy volunteers of both sexes. MATERIAL AND METHODS: The study was conducted open with randomized two-period crossover design and a 14-day washout period. Samples were obtained over a 48-hour interval. Glimepiride concentrations were analyzed by LC-MS-MS. From the glimepiride plasma concentration versus time curves the following pharmacokinetic parameters were obtained: AUC(0-last), AUC(0-t), AUC(0-infinity), Ke, T1/2, Cmax, and Tmax. RESULTS: Geometric mean of Glimepirida/Amaryl 4 mg was 102.35% for AUC(0-t), 102.35% for AUC(0-infinity) and 99.31% for Cmax. The 90% CI was 92.62-109.55%; 95.62-109.55% e 88.60-111.32%, respectively. CONCLUSION: Since the 90% CI for both Cmax, AUC(0-t), and AUC(0-infinity) were within the interval of 80-125%, it was concluded that both formulations were bioequivalent, according to both the rate and extent of absorption.
Assuntos
Hipoglicemiantes/farmacocinética , Compostos de Sulfonilureia/farmacocinética , Adulto , Disponibilidade Biológica , Cápsulas , Estudos Cross-Over , Feminino , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/sangue , Masculino , Valores de Referência , Compostos de Sulfonilureia/administração & dosagem , Compostos de Sulfonilureia/sangue , Equivalência TerapêuticaRESUMO
OBJETIVO: Comparar a biodisponibilidade de duas formulações de glimepirida em 26 voluntários sadios de ambos os sexos. MATERIAL E MÉTODOS: O estudo foi aberto, cruzado e randomizado com dois períodos e wash out de 14 dias. As amostras foram obtidas em um intervalo de 48 horas. As concentrações de glimepirida foram analisadas por HPLC MS/MS. Das curvas de concentração de glimepirida no plasma versus tempo, foram obtidos os seguintes parâmetros farmacocinéticos: ASC(0-t), ASC(0-∞), Cmax, Ke, Tmax e T1/2. RESULTADOS: A razão entre as média geométricas de Glimepirida/Amaryl® 4 mg foi de 102,35 por cento para ASC(0-t); 102,35 por cento para ASC(0-∞) e 99,31 por cento para Cmax. Os intervalos de confiança de 90 por cento (IC 90 por cento) foram de 92,62-109,55 por cento; 95,62-109,55 por cento e 88,60-111,32 por cento, respectivamente. CONCLUSÃO: Como o IC 90 por cento para Cmax, ASC(0-t) e ASC(0-∞) estava dentro do intervalo de 80-125 por cento, concluiu-se que ambas as formulações foram bioequivalentes de acordo com o grau e a extensão de sua absorção.
OBJECTIVE: To compare the bioavailability of two glimepiride 4-mg tablet formulation in 26 healthy volunteers of both sexes. MATERIAL AND METHODS: The study was conducted open with randomized two-period crossover design and a 14-day washout period. Samples were obtained over a 48-hour interval. Glimepiride concentrations were analyzed by LC-MS-MS. From the glimepiride plasma concentration versus time curves the following pharmacokinetic parameters were obtained: AUC(0-last), AUC(0-t), AUC(0-∞), Ke, T1/2, Cmax, and Tmax. RESULTS: Geometric mean of Glimepirida/Amaryl® 4 mg was 102.35 percent for AUC(0-t), 102.35 percent for AUC(0-∞) and 99.31 percent for Cmax. The 90 percent CI was 92.62-109.55 percent; 95.62-109.55 percent e 88.60-111.32 percent, respectively. CONCLUSION: Since the 90 percent CI for both Cmax, AUC(0-t), and AUC(0-∞) were within the interval of 80-125 percent, it was concluded that both formulations were bioequivalent, according to both the rate and extent of absorption.