Development and Validation of an RP‐HPLC Method for Organic Impurity Profiling in Baclofen Utilizing Robustness Through a Quality‐by‐Design (QbD) Approach: A Comprehensive Forced Degradation Assessment

Abstract

Strong understandings of science and risk evaluation methodologies are needed to design an analytical method for pharmaceutical quality assessment. This article provides an HPLC method for separating and quantifying baclofen and related impurities. The technique used a Waters Symmetry C₁₈ column, 250 × 4.6 mm, 5 μm in gradient mode. Mobile Phase A was prepared by dissolving 0.0128 M of 1-octane sulfonic acid sodium salt in water, followed by the addition of 1 mL of orthophosphoric acid and 2 mL of tetrabutylammonium hydroxide to make up to a solution of 1 L. Mobile Phase B was a homogenous mixture of methanol and water in a 900:100 (v/v) ratio. A 0.7-mL/min flow rate was maintained for 60 min. The sample cooler and column temperatures were kept at 25°C and 32°C with a 10-μL injection volume. The detecting wavelength was 225 nm. The drug product and material were subjected to acidity, base, oxidation, heat, and photolysis according to International Conference on Harmonization (Q2) criteria. A linear response (R² > 0.999), accuracy (recoveries 97.1%-102.5%), precision (RS ≤ 5.0%), sensitivity, and specificity were demonstrated by the proposed method. This method ensures reliable analytical performance by cleanly separating compounds. Final method conditions were assessed using a full-factorial design. Graphical optimization from the design space identified robust technique conditions.