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Validation of LC‐MS/MS method applied to evaluation of free tissue concentrations of vildagliptin in diabetic rats by microdialysis
Author(s) -
Andrade Cristiane,
Araújo Lock Graziela,
Pigatto Maiara Cássia,
Haas Sandra Elisa,
Costa Teresa Dalla,
Araújo Bibiana Verlindo
Publication year - 2014
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.3212
Subject(s) - vildagliptin , chemistry , microdialysis , chromatography , pharmacokinetics , bioanalysis , ammonium formate , ultrapure water , pharmacology , high performance liquid chromatography , diabetes mellitus , biochemistry , type 2 diabetes , medicine , materials science , extracellular , nanotechnology , endocrinology
A novel LC‐MS/MS method was developed for the quantification of vildagliptin in an aqueous matrix. The method was successfully validated, meeting all the requisites of US Food and Drug Administration guide for a bioanalytical method. The developed method presented a limit of quantification of 10 ng/mL and the range of concentration achieved was 10–1875 ng/mL. The injection volume necessary was only 10 μL, and retention time was 4.60 min. The mobile phase employed was methanol–ammonium acetate 5 m m (95:5). The stability of the drug was evaluated in the different conditions through which the samples passed. A pharmacokinetic experiment was conducted with diabetic male Wistar rats, and the concentration of drug in liver was evaluated through a microdialysis technique. The perfusion fluid employed was ultrapure water. The dose administrated was 50 mg/kg and the method allowed the quantification of vildagliptin for more than three half lives, successfully characterizing the pharmacokinetic profile when the developed method was applied. This is the first report on the tissue pharmacokinetics of a DPP‐4 inhibitor and could contribute to drug dosage optimization in the future. Copyright © 2014 John Wiley & Sons, Ltd.