LAUSR

The aim of this study was to establish and validate an alternative high-performance liquid chromatography (HPLC) method for simultaneous quantification of pyrazinamide, isoniazid, acetyl-isoniazid and rifampicin in plasma of patients under treatment for tuberculosis. The performed method was lineal (r2 >0.99) in the range of 2.00-50.00 μg/mL for pyrazinamide, 0.50-20.00 μg/mL for both acetyl-isoniazid and isoniazid, and 1.20-25.00 μg/mL for rifampicin. Precision and trueness were demonstrated with CV% <15% and deviations <15% respectively, for quality controls samples. The lower limit of quantification was 2.00, 0.50, 0.50 and 1.20 μg/mL for pyrazinamide, isoniazid, acetyl-isoniazid and rifampicin, respectively. The method was applied for the analysis of plasma from patients with tuberculosis. This method allowed ensuring reliable quantification of the target compounds and their pharmacokinetics parameters. In general, the mean values of maximum concentration of each anti-tuberculosis drug were located within their respective reference therapeutic ranges. However, patients with subtherapeutic plasma concentrations of isoniazid and rifampicin were detected. This is the first analytical technique that simultaneously quantifies isoniazid, acetyl-isoniazid, rifampicin, and pyrazinamide concentrations from plasma samples by HPLC with ultraviolet/visible. The proposed method could be applied for therapeutic drug monitoring and pharmacokinetics studies of the four compounds throughout the treatment of tuberculosis patients. This article is protected by copyright. All rights reserved.