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  2. A new HPLC-MS/MS method for the simultaneous quantification of SGLT2 inhibitors and metformin in plasma and its application to a pharmacokinetic study in healthy volunteers

A new HPLC-MS/MS method for the simultaneous quantification of SGLT2 inhibitors and metformin in plasma and its application to a pharmacokinetic study in healthy volunteers

  • Biomed Chromatogr. 2019 Nov;33(11):e4663. doi: 10.1002/bmc.4663.
Bruna Carolina Lui Dias 1 Mariana Millan Fachi 1 Michel Leandro de Campos 2 Flávia Lada Degaut Degaut 1 Rosângela Gonçalves Peccinini 3 Roberto Pontarolo 1
Affiliations

Affiliations

  • 1 Department of Pharmacy, Federal University of Parana, Curitiba, Paraná, Brazil.
  • 2 Federal University of Mato Grosso, Health Sciences Institute, Sinop, MT, Brazil.
  • 3 Department of Natural Active Principles and Toxicology, São Paulo State University (UNESP), School of Pharmaceutical Sciences, Araraquara, Brazil.
Abstract

Monitoring the plasma concentrations of metformin and sodium-glucose cotransporter-2 inhibitors (canagliflozin, dapagliflozin and empagliflozin) is essential for pharmacokinetic and bioequivalence studies and therapeutic monitoring. The present work therefore aimed to develop and validate a high-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) method for the simultaneous quantification of these drugs in human plasma. The analyses were performed using an Agilent 1200 HPLC system coupled to an Applied Biosystems API 3200 triple quadrupole MS/MS with electrospray ionization in positive ion mode. After one-step protein precipitation of plasma with acetonitrile containing 0.1% formic acid, chromatographic separation was achieved on an Xbridge C18 column, with a mobile phase consisting of a gradient of water and acetonitrile, both containing 1 mm ammonium formate and 0.1% formic acid. Quantification was performed in multiple reaction monitoring mode using m/z 130.1 → 71.1 for metformin, m/z 462.0 → 191.2 for canagliflozin, m/z 426.1 → 167.1 for dapagliflozin and m/z 468.0 → 354.9 for empagliflozin. The proposed method was validated and demonstrated to be adequate for the quantification of metformin, canagliflozin, dapagliflozin and empagliflozin for clinical monitoring, pharmacokinetics and bioequivalence studies.

Keywords

human plasma; metformin; pharmacokinetics; quantification; sodium-glucose cotransporter-2 inhibitor.

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