Analytical Method Development and Validation for a Fixed-Dose ALS Combination Using RP-HPLC: A QbD and Response Surface Optimization Approach

This study presents the development and optimization of a robust and reliable RP-HPLC method for the simultaneous estimation of Sodium Phenylbutyrate and Taurursodiol in a fixed-dose combination, guided by Quality by Design (QbD) principles. Sodium Phenylbutyrate, an ammonia scavenger, and Taurursodiol, a cytoprotective bile acid derivative, are used to treat neurodegenerative disorders such as ALS. A Central Composite Design (CCD) was employed to systematically evaluate the effects of acetonitrile ratio and flow rate on three critical responses: resolution between peaks (R۱), tailing factor of Sodium Phenylbutyrate (R۲), and Turursodiol (R۳). The method was optimized using a Waters X-Bridge Phenyl column with a mobile phase of acetonitrile: ۰.۱% orthophosphoric acid (OPA) (۳۰:۷۰), a flow rate of ۱.۰ mL/min, and detection at ۲۸۷ nm. The method exhibited excellent linearity (R² > ۰.۹۹۹), precision (%RSD < ۱%), and accuracy (recovery: ۹۸-۱۰۲%). Forced degradation studies confirmed its stability indicating capability. The optimized chromatographic conditions ensured high resolution and minimal tailing with satisfactory system suitability. This validated method provides a scientific basis for the quality control and routine analysis of neuroprotective agents in pharmaceutical formulations.

کلیدواژه ها:

Sodium Phenylbutyrate ، Taurursodiol ، RP-HPLC ، Quality by Design (QbD) ، Central composite design ، Method Validation