Analytical Method Development and Validation for a Fixed-Dose ALS Combination Using RP-HPLC: A QbD and Response Surface Optimization Approach
نویسندگان
1 Department of Pharmaceutics, Vels Institute of Science, Technology and Advanced Studies (VISTAS), PV Vaithiyalingam Rd, Velan Nagar, Krishna puram, Pallavaram, Chennai, 600 117, Tamil Nadu, India
2 Manager Analytical Chemistry, Elixir Medical Corporation, 920 N McCarthy Blvd #100, Milpitas, CA 95035, USA
3 Department of Pharmaceutics, Vels Institute of Science, Technology and Advanced Studies (VISTAS), PV Vaithiyalingam Rd, Velan Nagar, Krishna Puram, Pallavaram, Chennai, 600 117, Tamil Nadu, India
4 Department of Pharmaceutics, KVSR Siddhartha College of pharmaceutical sciences, Vijayawada, Andhra Pradesh India
5 Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Mysuru, Karnataka-570015, India
6 Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Mysuru, Karnataka-570015, India
7 Raghavendra Institute of Pharmaceutical Education and Research (RIPER)-Autonomous, Ananthapuramu, Andhra Pradesh, India
8 Department of Pharmacy Practice, School of Pharmaceutical Sciences, Vels Institute of Science, Technology and Advanced Studies (VISTAS), Pallavaram, Chennai 600 117, India
doi
10.48309/ajca.2025.522568.1844چکیده
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 (R1), tailing factor of Sodium Phenylbutyrate (R2), and Turursodiol (R3). The method was optimized using a Waters X-Bridge Phenyl column with a mobile phase of acetonitrile: 0.1% orthophosphoric acid (OPA) (30:70), a flow rate of 1.0 mL/min, and detection at 287 nm. The method exhibited excellent linearity (R² > 0.999), precision (%RSD < 1%), and accuracy (recovery: 98-102%). 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.
