Rapid and sensitive ultra-high-pressure liquid chromatography method for quantification of antichagasic benznidazole in plasma: application in a preclinical pharmacokinetic study

Autor(es)

Davanco, Marcelo Gomes ^[1] ; de Campos, Michel Leandro ^[1] ; Peccinini, Rosangela Goncalves ^[1]

Afiliação do(s) autor(es)

^[1] Sao Paulo State Univ, Dept Nat Act Principles & Toxicol, Sch Pharmaceut Sci, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: BIOMEDICAL CHROMATOGRAPHY; v. 29, n. 7, p. 1008-1015, JUL 2015.
• Citações Web of Science: 5

Resumo

Benznidazole (BNZ) and nifurtimox are the only drugs available for treating Chagas disease. In this work, we validated a bioanalytical method for the quantification of BNZ in plasma aimed at improving sensitivity and time of analysis compared with the assays already published. Furthermore, we demonstrated the application of the method in a preclinical pharmacokinetic study after administration of a single oral dose of BNZ in Wistar rats. A Waters (R) Acquity UHPLC system equipped with a UV-vis detector was employed. The method was established using an Acquity (R) UHPLC HSS SB C-18 protected by an Acquity (R) UHPLC HSS SB C-18 VanGuard guard column and detection at 324 nm(.) The mobile phase consisted of ultrapure water-acetonitrile (65:35), and elution was isocratic. The mobile phase flow rate was 0.55 mL/min, the volume of injection was 1 L, and the run time was just 2 min. The samples were kept at 25 degrees C until injection and the column at 45 degrees C for the chromatographic separation. The sample preparation was performed by a rapid protein precipitation with acetonitrile. The linear concentration range was 0.15-20 mu g/mL. The pharmacokinetic parameters of BNZ in rats were determined and the method was considered sensitive, fast and suitable for application in pharmacokinetic studies. Copyright (c) 2014 John Wiley \& Sons, Ltd. (AU)

• Processo FAPESP: 11/11239-9 - Farmacocinética pré-clínica de novos fármacos e medicamentos
• Beneficiário: Rosangela Gonçalves Peccinini
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 09/51075-5 - Farmacocinética pré-clínica de Phe-Ala-PQ - pró-fármaco potencialmente anti-chagásico
• Beneficiário: Marcelo Gomes Davanço
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica