UHPLC Quantitation Method for New Thiazolidinedione LPSF/GQ-02 and In Vitro/In Vivo Kinetic Studies

Title:UHPLC Quantitation Method for New Thiazolidinedione LPSF/GQ-02 and In Vitro/In Vivo Kinetic Studies

Volume: 10 Issue: 3

Author(s): Carla Monalizi Vieira, Michel Leandro de Campos, Elias Carvalho Padilha, Marina Pitta, Ivan da Rocha Pitta, Maria do Carmo Alves de Lima and Rosângela Gonçalves Peccinini

Affiliation:

Keywords: Bioanalytical method, LPSF/GQ-02, Preclinical pharmacokinetics, Safety assessment, Thiazolidinedione, UHPLC.

Abstract: Background: LPSF/GQ-02 is a promising benzylidene thiazolidinedione that has demonstrated antidiabetic, antidyslipidemic, anti-atherosclerotic properties and can also treat non-alcoholic fatty liver disease. Despite all activity studies of the new compound, its pharmacokinetics are not yet described.

Objective: The aim of this study was to perform its first pharmacokinetic profile.

Methods: For this purpose a bioanalytical method for the quantitation of 5-(4- Chloro-benzylidene)-3-(4-methylbenzyl)-thiazolidine-2,4-dione (LPSF/GQ-02) was developed and validated. A Waters UPLC chromatographer using a BEH column (2.1x50mm, 1.7μm particle), mobile phase water:acetonitrile (20:80) was used. The range of calibration curve in plasma was 1.9 to 250 ng/mL with r = 0.9997. LPSF/GQ-02 stability was evaluated in rat plasma and buffers at pH 1.2 and 7.4. The pharmacokinetic assay was carried out in male Wistar rats weighing 250-300 g. The animals received LPSF/GQ-02 at 3 mg/kg by intravenous route. The animals were used to perform a preliminary safety study concerning the evaluation of liver and kidney biomarkers (ALT, AST, urea, creatinine).

Results: The obtained pharmacokinetic parameters were elimination half-life of 4.44 h, Cl of 8.00 L/h.kg, Vd of 45.60 L/kg and MRT of 3.79h. No difference was observed for the liver and kidney biomarkers.

Conclusion: The intravenous pharmacokinetic parameters are in agreement with a good future posology, even though the plasma concentrations from oral administration were not quantifiable in a dose of 12 mg/kg. The preliminary safety study demonstrated no acute effect of the drug in liver and kidneys. The LPSF/GQ-02 is a new thiazolidinedione that should continue being evaluated for future clinical use.

Cite this article as:

Vieira Monalizi Carla, Campos Leandro de Michel, Padilha Carvalho Elias, Pitta Marina, Pitta da Rocha Ivan, Lima do Carmo Alves de Maria and Peccinini Gonçalves Rosângela, UHPLC Quantitation Method for New Thiazolidinedione LPSF/GQ-02 and In Vitro/In Vivo Kinetic Studies, Drug Metabolism Letters 2016; 10 (3) . https://dx.doi.org/10.2174/1872312810666160725124554