Comparative greenness assessment of analytical methods for the estimation of amlodipine besylate and indapamide using green analytical chemistry principles

The increasing emphasis on environmental sustainability has necessitated the integration of green analytical chemistry (GAC) principles into pharmaceutical analysis. This review critically evaluates the greenness of various analytical methods developed for the simultaneous estimation of amlodipine besylate and indapamide in pharmaceutical formulations and biological matrices. Techniques such as spectrophotometry, RP-HPLC, HPTLC, and UPLC–MS/MS were compared using greenness assessment tools such as the Analytical Eco-Scale and the Analytical GREEnness (AGREE) metric. Spectrophotometric methods emerged as the most eco-friendly, attributed to their minimal reagent use, absence of buffers, low energy requirements, and negligible waste generation. HPTLC methods utilizing greener solvents such as ethanol and ethyl acetate also demonstrated favorable greenness profiles while maintaining analytical reliability. RP-HPLC methods, though robust and precise, were found to generate significant solvent waste and consume high energy, especially when employing phosphate buffers and high flow rates. UPLC–MS/MS methods, despite their superior sensitivity and specificity, scored lower on greenness metrics due to high energy demands and complex solvent systems. Analytical Quality by Design (AQbD) driven method optimization in RP-HPLC showed promise in enhancing environmental compliance. This review highlights the need for adopting GAC principles during analytical method development and encourages the pharmaceutical industry to transition toward more sustainable, greener analytical practices without compromising method performance.