Hydrophilic Interaction Liquid Chromatography-Electrospray Ionization Mass Spectrometry for Therapeutic Drug Monitoring of Metformin and Rosuvastatin in Human Plasma

Molecules. 2018 Jun 27;23(7):1548. doi: 10.3390/molecules23071548.


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.

Keywords: HILIC; LC-MS; metformin; rosuvastatin; therapeutic drug monitoring.

MeSH terms

  • Chromatography, Liquid / methods*
  • Humans
  • Metformin / blood*
  • Rosuvastatin Calcium / blood*
  • Spectrometry, Mass, Electrospray Ionization / methods*


  • Rosuvastatin Calcium
  • Metformin