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A valine carbamate prodrug of naringenin (NAR) called 4'V was synthesized to enhance its oral bioavailability because of low water solubility and poor membrane permeability of NAR. This study developed and fully validated a sensitive, rapid, and robust HPLC-MS/MS method for the simultaneous determination of NAR and 4'V in plasma. The analytes were treated using liquid-liquid extraction, separated on a Phenomenex Kinetex XB-C18 column, and detected using a triple-quadrupole tandem mass spectrometer equipped with an electrospray ionization