From design space to green space: an analytical quality by design–assisted high-performance liquid chromatography method for the quantification of triple-combination antihypertensive drugs

To develop a reliable, High-performance Liquid Chromatography technique for the simultaneous determination of a Fixed-Dose Combination of hydrochlorothiazide, amlodipine besylate, and telmisartan. The concepts of Green Analytical Chemistry and Analytical Quality by Design are combined in this work. For optimal results, Shim-pack C18 (4.6 × 250 mm, 5 µm particle size) was utilized. With an injection volume of 20 µL, a gradient of isopropanol: acetate buffer (0.1 M, pH 5.8) as a buffer, at a flow rate of 1.075 mL/min, and UV detection at 324 nm, the mobile phase was composed. The retention times for hydrochlorothiazide (HCT), amlodipine besylate (AML), and telmisartan (TEL) were found to be 3.192, 4.515, and 5.097 min, respectively. All parameters, including relative standard deviation, accuracy, precision, linearity, robustness, and specificity, were examined and found to be less than 2% for the proposed approach. Dong's algorithm computations have identified and verified the areas where the method's optimization is carried out in the design space allotted to the developed method for estimating these drugs in combination dose forms. The developed method was validated and found to be successful in identifying the three drugs in commercially available tablets. In addition to this the method sustainability was assessed with a comprehensive multi-parameter evaluation adopting various sustainability assessment tools including carbon footprint estimation and mobile phase greenness assessment using the Green Environmental Assessment and Rating for Solvents (GEARS), and environmental impact indices such as the Red Analytical Performance Index (RAPI), Click Analytical Chemistry Index (CACI), Blue Applicability Grade Index (BAGI), Modified Green Analytical Procedure Index (MoGAPI), Analytical GREEnness prep (AGREEprep), Analytical Green Star Area (AGSA), and RGBfast. The collective outcomes of these assessments demonstrated that the proposed method is environmentally benign, as it employs fewer hazardous chemicals, generates reduced waste, and requires lower energy consumption.