Validation of LC-MS/MS method applied to evaluation of free tissue concentrations of vildagliptin in diabetic rats by microdialysis.
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 mm (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.
Programa de Pós-Graduacão em Ciências Farmacêuticas, UniversidadeFederal do Rio Grande do Sul, Av. Ipiranga, 2752, Porto Alegre CEP, 90610-000, RS, Brazil.
Cristiane
C
de Andrade
Graziela
G
de Araújo Lock
Maiara Cássia
MC
Pigatto
Sandra Elisa
SE
Haas
Teresa Dalla
TD
Costa
Bibiana Verlindo
BV
de Araújo
D000218:Adamantane / Q000031:analogs & derivatives* / Q000032:analysis / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000032:analysis / Q000737:chemistry / Q000493:pharmacokinetics; D004355:Drug Stability; D008099:Liver / Q000737:chemistry; D008297:Male; D017551:Microdialysis / Q000379:methods*; D009132:Muscles / Q000737:chemistry; D009570:Nitriles / Q000032:analysis* / Q000737:chemistry / Q000493:pharmacokinetics; D011759:Pyrrolidines / Q000032:analysis* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods; D014018:Tissue Distribution; D000077597:Vildagliptin
D054873:Dipeptidyl-Peptidase IV Inhibitors; D009570:Nitriles; D011759:Pyrrolidines; D000077597:Vildagliptin; D000218:Adamantane
DPP-4 inhibitor; LC-MS/MS; microdialysis; pharmacokinetics; vildagliptin