Development and Validation of a Derivatization-Based Spectrophotometric Procedure for Pregabalin Determination

Abstract: In this study, a sensitive, rapid, economical, and simple derivatization-based spectrophotometric procedure was developed and validated for the determination of pregabalin in bulk substance and pharmaceutical formulations. The procedure is based on the formation of a chromogenic imine derivative through the reaction of the primary amine group of pregabalin with 2-naphthaldehyde in a basic medium. Experimental design methodology was applied to screen and optimize the critical reaction parameters, including K2CO3 concentration, temperature, and ethanol volume. A central composite design was employed to evaluate factor effects and to establish the optimal derivatization conditions. After derivatization, absorbance measurements were performed at 228 nm in the UV spectrum and at 236 nm for the first-derivative spectrophotometric mode. The procedure showed linearity in the concentration range of 2–30 µg/mL for the direct UV measurement and 2–50 µg/mL for the first-derivative measurement, with coefficients of determination greater than 0.999. The analytical performance of the procedure was validated according to ICH Q2(R1) guidelines with respect to linearity, precision, accuracy, limits of detection and quantification, and stability. The results demonstrate that the proposed derivatization-based spectrophotometric procedure provides a reliable, reproducible, and cost-effective alternative for the quantitative analysis of pregabalin in pharmaceutical quality control laboratories.