Stability and Kinetics Studies Using an RP- HPLC-UV Method Developed for Assays of Salvianolic Acid A Degradation as a Therapeutic

Aims: To evaluate the stability of Salvianolic acid A (SAA), a promising cardiovascular drug candidate. Additionally avail an archetype in-vitro therapeutic monitoring from SAA degradation profile for characteristic oral gavages.

Study Design: Experimental by laboratory analysis.

Place and Duration of Study: Department of Chemistry & Biochemistry, Moi University; Department of Pure & Applied Chemistry and Department of Medical Laboratory Sciences of Masinde Muliro University of Science & Technology, between June 2013 and September 2014.

Methodology: Drug stability was studied according to ICH guidelines. A stability-indicating HPLC method was developed and validated; mimicking the systemic environs SAA degradation kinetics was then evaluated.

Results: SAA degradation followed first-order kinetics with rate constant increasing from 0.0099 h−1 at 313 K to 0.08044 h−1 at 363 K. The t0.5 was between 70.0 and 9.8 hours while t0.9 was between 10.6 and 1.5 hours within 313 K to 363K temperature range. Activation energy was 39.56 KJmol-1. A V-shaped pH-rate profile was observed with maximum stability at pH4.0. Degradation was rapid in hydrogen peroxide solution and in the simulated gastro-intestinal fluids. SAA exhibits high stability at pH 4.0, hence the suggested optimum pH for processing.

Conclusion: This study provides sufficient physicochemical data depicting SAA to be of intermediate stability. Therefore availing an imperative basis for selecting suitable dosage forms and expected kinetics during therapeutic SAA monitoring.