¹University of Health Science and Pharmacy in St. Louis, Department of Pharmaceutical and Administrative Sciences, St. Louis, MO, United States DOI : 10.29228/jrp.708 The primary goal of this study was to develop and validate an LC-MS/MS method for the detection of dapagliflozin in nanostructured lipid carriers (NLC) using ion-interaction chromatography. The reversed-phase InfinityLab Poroshell 120 (150 × 4.6 mm, 4 μm) column, using a mobile phase of acetonitrile-25 mM ammonium acetate solution with pH 4.1 (35:65, v/v), effectively separated the analytes and their internal standards. This method has been thoroughly tested and validated to ensure accurate and reliable results. To improve sensitivity and selectivity, mass spectrometry was used in polarity switching mode. In order to study ion transitions for dapagliflozin in both positive and negative mode, multiple reaction monitoring mode was utilized, with the ion transitions being m/z 467.1 [M+CH3COO]- /329.1. The assay's linear calibration range for dapagliflozin was established from 0.05-150 ng/mL to improve drug pharmacokinetics assessment. The analyte's limit of detection (LOD) and limit of quantitation (LOQ) were 0.07 and 0.35 ng/mL, respectively. After testing, no interference was observed in plasma matrices from different sources, including haemolysed and lipemic plasma. The impact of Dapagliflozin-loaded NLC on plasma levels were investigated using this method. Keywords : Nanostructured lipid carriers; quantitative method; SGLT-2 inhibitors; dapagliflozin; plasma extraction