[Simultaneous determination of metformin and glipizide in human plasma by liquid chromatography-tandem mass spectrometry].

To develop a sensitive and rapid liquid chromatographic-tandem mass spectrometric (LC-MS/MS) method for simultaneous quantitation of metformin and glipizide in human plasma, metformin, glipizide and internal standard diphenhydramine were separated from plasma by protein precipitation with acetonitrile (containing 0.3% formic acid), then chromatographed by using a Zorbax Extend C18 column. The mobile phase consisted of acetonitrile-water-formic acid (70:30: 0.3, v/v/v), at a flow rate of 0.50 mL x min(-1). A tandem mass spectrometer equipped with atmospheric pressure chemical ionization source was used as detector and operated in the positive ion mode. Selected reaction monitoring (SRM) using the precursor/production combinations of m/z 130-->m/z 60, m/z 446-->m/z 321 and m/z 256-->m/z 167 were used to quantify metformin, glipizide and diphenhydramine, respectively. The linear concentration ranges of the calibration curves for metformin and glipizide were 2.00 - 2000 ng x mL(-1) and 1.00 - 1000 ng x mL(-1), respectively. The lower limits of quantitation of metformin and glipizide were 2.00 ng x mL(-1) and 1.00 ng x mL(-1), respectively. The method proved to be sensitive, simple and rapid, and suitable for clinical investigation of compound preparation containing metformin and glipizide.