title: Simultaneous determination of metformin and vildagliptin in human plasma by a HILIC-MS/MS method.
abstract: The objective of this work was to develop and validate a HILIC-MS/MS method for the simultaneous determination of metformin and vildagliptin in human plasma. Chromatographic separation was achieved using an Atlantis HILIC Silica 150-mm × 2.1-mm, 3-μm particle size column maintained at 40°C. The isocratic mobile phase consisted of 20% water and 80% acetonitrile/water solution 95:5 (v/v), containing both 0.1% formic acid and 3mM ammonium formate. The flow rate was maintained at 400 μL min(-1). Data from validation studies demonstrated that the new method is highly selective, sensitive (limits of detection <1.5 ng mL(-1)) and free of matrix and residual effects. The new method was also precise (RSD<9.0%), accurate (RE<11.2%) and linear (r ≥ 0.99) over the ranges of 5-500 ng mL(-1) for each compound. The developed method was successfully applied to determine metformin and vildagliptin in plasma volunteers who orally received a single dose of metformin (850 mg), vildagliptin (50mg) or drug association (metformin 850 mg+vildagliptin 50mg). The new method can thus also be used as a tool for the clinical monitoring of metformin and vildagliptin.
authors.affiliation: Universidade Federal do Paraná, Department of Pharmacy, 632 Lothário Meissner Avenue, 80210-170, Curitiba - PR, Brazil. Electronic address: pontarolo@ufpr.br.
authors.forename: Roberto
authors.initials: R
authors.lastname: Pontarolo
authors.affiliation: Universidade Federal do Paraná, Department of Pharmacy, 632 Lothário Meissner Avenue, 80210-170, Curitiba - PR, Brazil.
authors.forename: Ana Carolina
authors.initials: AC
authors.lastname: Gimenez
authors.affiliation: Universidade Federal do Paraná, Department of Pharmacy, 632 Lothário Meissner Avenue, 80210-170, Curitiba - PR, Brazil.
authors.forename: Thais Martins Guimarães
authors.initials: TM
authors.lastname: de Francisco
authors.affiliation: Universidade Federal do Paraná, Department of Pharmacy, 632 Lothário Meissner Avenue, 80210-170, Curitiba - PR, Brazil.
authors.forename: Rômulo Pereira
authors.initials: RP
authors.lastname: Ribeiro
authors.affiliation: Universidade Federal do Paraná, Department of Pharmacy, 632 Lothário Meissner Avenue, 80210-170, Curitiba - PR, Brazil.
authors.forename: Flávia Lada Degaut
authors.initials: FL
authors.lastname: Pontes
authors.affiliation: Universidade Federal do Paraná, Department of Pharmacy, 632 Lothário Meissner Avenue, 80210-170, Curitiba - PR, Brazil.
authors.forename: João Cleverson
authors.initials: JC
authors.lastname: Gasparetto
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry; D000328:Adult; D002853:Chromatography, Liquid / Q000379:methods*; D004355:Drug Stability; D005260:Female; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D057230:Limit of Detection; D016014:Linear Models; D008297:Male; D008687:Metformin / Q000097:blood* / Q000737:chemistry; D008875:Middle Aged; D009570:Nitriles / Q000097:blood* / Q000737:chemistry; D011759:Pyrrolidines / Q000097:blood* / Q000737:chemistry; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*; D000077597:Vildagliptin
chemical_list: D009570:Nitriles; D011759:Pyrrolidines; D008687:Metformin; D000077597:Vildagliptin; D000218:Adamantane
keywords: HILIC; Human plasma; LC–MS/MS; Metformin; Vildagliptin