Simultaneous determination of metformin and glipizide in human plasma by liquid chromatography–tandem mass spectrometry

Abstract A method has been developed for the simultaneous quantification of metformin (I) and glipizide (II) in human plasma. It is based on high‐performance liquid chromatography with electrospray ionization tandem mass (LC‐ESI‐MS/MS) spectrometric detection in positive ionization mode. Phenformin (III) and gliclazide (IV) were used as internal standards for I and II, respectively. The MS/MS detection was performed in multiple reaction monitoring (MRM) mode. The precursor‐product ion combinations of m / z 130 → 71, 446 → 321, 206 → 60 and 324 → 127 were used to quantify I, II, III and IV, respectively. This method was validated in the concentration ranges of 0.02–4 µg/mL for I and 0.004–0.8 µg/mL for II. It was utilized to support a clinical pharmacokinetic study after single dose oral administration of a combination of I and II. Copyright © 2007 John Wiley & Sons, Ltd.