Human plasma concentrations of metformin HCl and dapagliflozin
l-proline were determined using LC–MS/MS methods. To measure the concentrations of metformin HCl, the LC–MS/MS system consisted of a
Micromass Quattro micro API (Waters) coupled with a
Waters ACQUITY UPLCTM (Waters). Samples were prepared by protein precipitation with acetonitrile. Chromatographic separation was achieved on an ACQUITY UPLC
® BEH HILIC Silica (2.1 mm × 50 mm, 1.7 μm) (Waters) with an isocratic solvent system. Using electron spray ionization in the positive ion mode with mass transitions, the mass spectrometer was operated at
m/
z 130.1→59.9 for metformin HCl and
m/
z 136.2→59.9 for metformin HCl-
d6 (IS). The calibration range of metformin HCl in plasma was 20–5000 ng/mL. The process parameters to determine dapagliflozin
l-proline concentrations were the same as those for metformin HCl. Using electron spray ionization in the positive ion mode with mass transitions, the mass spectrometer was operated at
m/
z 426.2→167.1 for dapagliflozin
l-proline and
m/
z 431.2→167.1 for dapagliflozin
l-proline-
d5 (IS). The calibration range of dapagliflozin
l-proline in the plasma was 1–400 ng/mL.
Chun M.H., Kim J.Y., Park E.S, & Choi D.H. (2021). Development of a Robust Control Strategy for Fixed-Dose Combination Bilayer Tablets with Integrated Quality by Design, Statistical, and Process Analytical Technology Approach. Pharmaceutics, 13(9), 1443.