Multicomponent Analysis of Antihyperlipidemic Drugs: Integrating Analytical Quality by Design and Multi‐Metric Green Liquid Chromatography

ABSTRACT Cardiovascular diseases remain a leading cause of mortality, and these are frequently treated with a combined therapy of statins and fenofibrate (FFB) in the treatment of lipids, which reveals a synergic effect. The primary aim of this study was to develop and validate a robust high‐performance liquid chromatography (HPLC) method for the quantification of pravastatin, rosuvastatin, atorvastatin, and FFB in bulk and solid oral dosage forms based on analytical quality by design (AQbD) and comprehensive green analytical chemistry (GAC) metrics. Systematic optimization was carried out by central composite design (CCD) experiment. The chromatographic separation was achieved using a Waters Sunfire C18 column (150 × 4.6 mm 2 , 5 µm) with 0.1% acetic acid: acetonitrile (23:77 v/v) as the mobile phase, a flow rate of 0.9 mL/min, and UV detection at 250 nm. The method was validated in accordance with ICH Q2(R2) guidelines. Moreover, the ecological and practical consequences of the procedure were assessed using a multi‐metric suite of GAC tools, including analytical Eco‐Scale, green analytical procedure index (GAPI), Analytical GREEnness (AGREE), red analytical performance index (RAPI), blue applicability grade index (BAGI), and analytical green star area (AGSA). The optimized experimental design allowed baseline separation of all four targeted drugs in an analysis time of less than 10 min. The validated method showed good linearity ( R 2 > 0.999) and high precision and accuracy, with recovery rates ranging from 98.21% to 99.67% for all analytes. The multi‐metric sustainability assessment gave an analytical Eco‐Scale score of 90, indicating the procedure is an excellent green analysis by supporting the use of minimal hazardous solvents and reducing energy consumption without loss of analytical efficiency. The method was successfully used to quantitatively evaluate the commercial binary formulations. This powerful and high‐throughput chromatographic method combines the benefits of statistical optimization and a comprehensive multidimensional greenness evaluation, making it an ideal and eco‐friendly solution for regular quality control testing of complex antihyperlipidemic combination products.