Application of advanced environmentally benign assessment tools in determining ternary cardiovascular drug combination by RP-HPLC with analytical quality by design: Application to stability indicating method evaluation

Abstract

Assessing any analytical method is becoming an important aspect for showcasing its importance and impact on the environment. The present work aimed to showcase different advanced tools available that need to be applied to analytical methods and make their developed methods essential for sustainable development. The work discussed the method development and validation of fixed combination of cardiovascular drugs, namely, cilnidipine (CIL), telmisartan (TEL), and chlorthalidone (CLD), using ICH Q14 (Recent amendment). Further application of stress studies in different conditions followed by application of recently developed assessment tools to determine the developed methodology. The developed method was optimized by using the rotatable quality by design approach, and the final optimized conditions for the separation of the mentioned drugs were performed on the Eclipse plus RP-HPLC column (C18 250 × 4.6 mm (i.d), 5 μm), with a gradient-elution mobile phase consisting of the ethanol and phosphate buffer (0.01 M, pH 3.5). Initially, the mobile phase composition was set at 40: 60. v/v (ethanol: buffer), then changed to 70: 30, v/v at 4.66 min. With a constant flow rate of 1.103 mL/min. The development method had a linearity concentration of 12.5–37.5 μg/mL for CLD, 40.0–120.0 μg/mL for TEL, and 10.0–30.0 μg/mL for CIL with a correlation coefficient (r) 0.9991, 0.9993 and 0.9991, respectively. The results of the degradation study revealed that the drugs degraded under stressed conditions, and the degradation products were separated using the same method. The degradation results indicated that the drugs degraded in stressful environments and that the degradation products have also been separated successfully using the same method. The application of greenness and whiteness evaluation tools provided comprehensive insights into the environmental impact and sustainability of the suggested methodology. The findings confirmed its favourable performance in terms of eco-friendliness and highlighted its alignment with sustainable practices. Further strengthens the credibility and relevance of the developed method in promoting a greener and more sustainable future.