Hydrophilic Interaction Liquid Chromatography-Electrospray Ionization Mass Spectrometry for Therapeutic Drug Monitoring of Metformin and Rosuvastatin in Human Plasma
Nikolaos Antonopoulos,
Giorgos Machairas,
George Migias,
Ariadni Vonaparti,
Vasiliki Brakoulia,
Constantinos Pistos,
Dimitra Gennimata,
Irene Panderi
Affiliations
Nikolaos Antonopoulos
Laboratory of Pharmaceutical Analysis, School of Pharmacy, Division of Pharmaceutical Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis, Zografou, 15771 Athens, Greece
Giorgos Machairas
Laboratory of Pharmaceutical Analysis, School of Pharmacy, Division of Pharmaceutical Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis, Zografou, 15771 Athens, Greece
George Migias
General Hospital of Athens Alexandra, 80 Vas. Sofias Avenue, 11528 Athens, Greece
Laboratory of Pharmaceutical Analysis, School of Pharmacy, Division of Pharmaceutical Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis, Zografou, 15771 Athens, Greece
Constantinos Pistos
Department of Chemistry, West Chester University, West Chester, PA 19383, USA
Dimitra Gennimata
General Hospital Korgialenio-Benakio National Red Cross, Erithrou Stavrou 1, 11526 Athens, Greece
Irene Panderi
Laboratory of Pharmaceutical Analysis, School of Pharmacy, Division of Pharmaceutical Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis, Zografou, 15771 Athens, Greece
In this work a hydrophilic interaction liquid chromatography/positive ion electrospray mass spectrometric assay (HILIC/ESI-MS) has been developed and fully validated for the quantitation of metformin and rosuvastatin in human plasma. Sample preparation involved the use of 100 μL of human plasma, following protein precipitation and filtration. Metformin, rosuvastatin and 4-[2-(propylamino) ethyl] indoline 2 one hydrochloride (internal standard) were separated by using an X-Bridge-HILIC BEH analytical column (150.0 × 2.1 mm i.d., particle size 3.5 μm) with isocratic elution. A mobile phase consisting of 12% (v/v) 15 mM ammonium formate water solution in acetonitrile was used for the separation and pumped at a flow rate of 0.25 mL min−1. The linear range of the assay was 100 to 5000 ng mL−1 and 2 to 100 ng mL−1 for metformin and rosuvastatin, respectively. The current HILIC-ESI/MS method allows for the accurate and precise quantitation of metformin and rosuvastatin in human plasma with a simple sample preparation and a short a chromatographic run time (less than 15 min). Plasma samples from eight patients were further analysed proving the capability of the proposed method to support a wide range of clinical studies.
