Analytical Development and Validation of a Reverse-Phase HPLC Method for the Determination of Pregabalin in Immediate-Release Capsules

Abstract

A simple, accurate, precise, and stability-indicating reverse-phase high-performance liquid chromatography (RP-HPLC) method was developed and validated for the quantitative determination of pregabalin in immediate-release capsule formulations. Chromatographic separation was achieved using an Inertsil ODS C18 column (250 × 4.6 mm, 5 μm) with gradient elution comprising phosphate buffer (pH 5.9) and acetonitrile as the mobile phase. Detection was carried out at 210 nm, with pregabalin eluting at a retention time of approximately 12.05 min. The method was validated according to the International Council for Harmonisation (ICH) Q2(R2) guidelines by evaluating system suitability, specificity, linearity, precision, intermediate precision, limits of detection (LOD) and quantification (LOQ), LOQ precision, robustness, analytical solution stability, filter compatibility, and forced degradation. The method exhibited excellent specificity without interference from blank, placebo, excipients, or degradation products. A linear response was obtained over the concentration range of 10–150%, with a correlation coefficient (R²) of 0.9983. The LOD and LOQ were determined to be 1.859 ppm and 5.633 ppm, respectively, demonstrating satisfactory sensitivity. Precision studies showed low percentage relative standard deviation (%RSD), confirming the method's repeatability and reproducibility, while robustness testing indicated consistent performance under deliberate variations in chromatographic conditions. Forced degradation studies under acidic, alkaline, and oxidative conditions confirmed the stability-indicating nature of the method by effectively resolving pregabalin from its degradation products. The validated RP-HPLC method is reliable, sensitive, and suitable for routine quality control, release testing, and stability studies of pregabalin immediate-release capsule formulations.