Efficient integration of analytical quality-by-design and tri-hued HPLC-DAD approach for synchronized assessment of gemigliptin and rosuvastatin in their fixed-dose pills: Application to stability study

Abstract

Life-threatening atherosclerotic cardiovascular disorder is a well-recognized risk among diabetics, which is clinically ascribed to their unbalanced plasma lipoproteins. Gemigliptin-Rosuvastatin is a recently introduced polytherapy prescribed for the management of diabetic dyslipidemia. Currently, the main focus of several analysts is to design more ecologically friendly sustainable approaches for pharmaceutical analysis. In this context, an innovative tri-hued (green, blue, and white) stability-indicating HPLC-DAD approach was developed to concurrently quantify Gemigliptin and Rosuvastatin polypills. Consequently, a strategic integration between analytical quality-by-design and green/white analytical chemistry principles was specifically designed to optimize efficiency and practicality while minimizing ecological burden. Two experimental designs, namely two-level fractional factorial and Box-Behnken designs, were employed for screening and optimization procedures, respectively. Optimal separation was attained utilizing an Agilent HC-C18 column in conjunction with a mobile phase consisting of acetonitrile and 10 mM sodium dihydrogen phosphate buffer, pH 3 (60:40 v/v), eluted in an isocratic manner at a 1 mL/min flow rate. Both analytes exhibited good linearities within the concentration range of 0.5–100 μg/mL. Furthermore, stability studies were conducted on both drugs in response to variable stress degradation scenarios. Fortunately, the adopted approach was well-suited to resolve the studied drugs from their respective degradants, thereby verifying the method's stability-indicating power. Tri-hued evaluation for the implemented approach was performed via up-to-date metrics, specifically, the Analytical Eco-scale, AGREE, Blue Applicability Grade Index, and RGB 12. Ultimately, our adopted stability-indicating HPLC approach exhibited great sensitivity, specificity, applicability, and rapidity as well as being ecologically sound. It is worth noting that this is the first stability-indicating HPLC approach for simultaneous assessment of the studied drugs.