Resolution of Creatinine Interference in Dexamethasone Sodium Phosphate Injectable Preparations: A Validated First-Order Derivative Spectrophotometric Method Using Matrix Matching and Zero-Crossing Point Interpolation

Background: The quantification of Dexamethasone Sodium Phosphate (DSP) in injectable formulations is significantly hindered by the spectral overlap of the stabilizer creatinine within the UV region. This study aims to develop a green first-order derivative (D1) spectrophotometric method to resolve this analytical challenge. Methods: Distilled water was utilized as a sustainable solvent, aligning with green chemistry principles. To ensure high specificity, a matrix-matching calibration strategy with a constant 1:2 (w/w) DSP:creatinine mass ratio across the entire concentration range was employed. DSP was determined using the zero-crossing technique, measuring the D1 amplitude at λZC ≅ 231.3 nm, where the creatinine contribution is nullified. Results: Linearity was established for DSP concentrations between 4.0–16.0 μg/mL (R2 > 0.99). Method validation, as per ICH Q2 (R1) guidelines (International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use), demonstrated excellent accuracy (mean recovery of 99.85%) and precision (RSD < 2%). Conclusions: The proposed method offers a rapid, cost-effective, and eco-friendly alternative for the routine quality control of DSP injectables, eliminating the necessity for complex chromatographic separation techniques.