Development and Validation of an RP-HPLC Method for Organic Impurity Profiling in Baclofen Utilizing Robustness...

Area of Science:

• Pharmaceutical Analysis
• Analytical Chemistry
• Quality Control

Background:

• Pharmaceutical quality assessment requires robust analytical methods.
• Risk evaluation is crucial for designing effective quality control techniques.
• Accurate quantification of active pharmaceutical ingredients and impurities is essential.

Purpose of the Study:

• To develop and validate a High-Performance Liquid Chromatography (HPLC) method for the separation and quantification of baclofen and its related impurities.
• To ensure reliable analytical performance for pharmaceutical quality assessment.

Main Methods:

• Utilized a Waters Symmetry C18 column (250 × 4.6 mm, 5 μm) in gradient mode.
• Employed specific mobile phases (A: 1-octane sulfonic acid sodium salt, orthophosphoric acid, tetrabutylammonium hydroxide in water; B: methanol/water 900:100 v/v).
• Optimized flow rate (0.7 mL/min), temperatures (25°C sample, 32°C column), and detection wavelength (225 nm) with full-factorial design.

Main Results:

• Demonstrated excellent linearity (R² > 0.999), accuracy (97.1%-102.5% recovery), and precision (RS ≤ 5.0%).
• Method proved sensitive and specific, with clean separation of baclofen and impurities.
• Stress testing (acidity, base, oxidation, heat, photolysis) confirmed method stability according to ICH Q2 criteria.

Conclusions:

• The developed HPLC method provides reliable and robust analytical performance for baclofen pharmaceutical quality assessment.
• Graphical optimization identified stable method conditions within the design space.
• This validated method is suitable for routine analysis and quality control of baclofen products.