Validation of LC‐MS/MS method applied to evaluation of free tissue concentrations of vildagliptin in diabetic rats by microdialysis

Abstract

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.

Realgar nanoparticle-based microcapsules: preparation and in-vitro/in-vivo characterizations

“…Pharmacokinetic studies were performed in normal, healthy, male Wistar rats. [13] The rats were divided into three groups (n = 6), and were administered CR, RN and RNM suspensions orally at a dose of 50 mg As2S2/kg body weight using a gavage needle. After administration, about 0.5 ml blood sample was collected from the ocular vein into a haeparinized tube in accordance with a programmed schedule at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36 and 48 h. The collected samples were dispelled using microwave and then assessed by HGAAS method.…”

Development and Validation of LC–MS/MS Method for Simultaneous Determination of Metformin and Four Gliptins in Human Plasma

“…Linagliptin was reported to be quantitatively analyzed using HPLC [32] and LC-MS/MS [33,34] techniques. Metformin and alogliptin in combined formulation were estimated by HPLC [35,36], whereas vildagliptin was analyzed by different chromatographic methods using LC-MS/MS [37] and reverse phase-HPLC [38,39]. In addition to that, HPLC methods for the simultaneous determination of more than one DPP-4 inhibitors in dosage forms have also been reported in the literature [40,41].…”

A Microdialysis in Adjuvant Arthritic Rats for Pharmacokinetics–Pharmacodynamics Modeling Study of Geniposide with Determination of Drug Concentration and Efficacy Levels in Dialysate

“…The technology is time-resolved and space-resolved, providing free small-molecule compounds. Microdialysis for use in PK and PD research has been applied and developed, and a large amount of literature has been reported [ 19 , 20 , 21 , 22 ].…”