Chemists have developed and validated a reversed-phase high-performance liquid chromatography method that determines rosuvastatin, atorvastatin, and ezetimibe simultaneously in pharmaceutical formulations. The work, published open access in BMC Chemistry, addresses a practical analytical challenge: these three drugs have distinct physicochemical properties, which makes measuring them together in a single run difficult.
The method was guided by Analytical Quality by Design, an approach in which critical method parameters are systematically optimized rather than adjusted by trial and error. The team used a Box-Behnken design and response surface methodology to tune three parameters: the concentration of the chaotropic agent potassium hexafluorophosphate, the column temperature, and the acetonitrile fraction of the mobile phase.
The optimized conditions comprised a 0.2 mM KPF6 aqueous buffer, a column temperature of 48 °C, and a 60% acetonitrile mobile phase. Under these conditions, the three analytes were efficiently separated, with the most lipophilic compound, atorvastatin, retained at 2.29 minutes.
The method was validated as stability-indicating, meaning it can distinguish intact drugs from their degradation products. Analytical performance met standard quality control criteria: linearity with r² of at least 0.996 over a range of 12.0 to 50.0 µg/mL, accuracy of 98 to 102% recovery, and precision with relative standard deviations below 2%.
A notable feature of the study is its quantitative assessment of environmental sustainability. The authors applied multiple greenness and practicality metrics, reporting scores of 0.61 for AGREE, 75 for MoGAPI, 63.89 for AGSA, 70 for CACI, 72 for CaFRI, and 80.0 for BAGI.
The combination of speed, robustness, and green credentials matters for routine pharmaceutical quality control. Laboratories analyzing pharmaceutical formulations containing rosuvastatin, atorvastatin, and ezetimibe can use this single rapid chromatographic method for simultaneous determination of the three drugs, and the authors report quantitative greenness and practicality metric scores supporting its environmental favorability.
The article was published on 12 October 2026 and is currently available as a peer-reviewed, accepted manuscript shared early for faster access; this version remains subject to further edits before the final Version of Record replaces it.
Within the scope of the reported validation, the authors conclude that the AQbD-guided RP-HPLC method is rapid, reliable, robust, and environmentally favorable, and is highly suitable for routine quality control of pharmaceutical formulations containing the three drugs. As with any validated analytical method, its performance figures apply to the studied concentration range and matrix, and routine laboratories would be expected to confirm suitability within their own systems.
Subject of Research: Development and validation of a green, AQbD-guided RP-HPLC method for simultaneous determination of rosuvastatin, atorvastatin, and ezetimibe
Article Title: A chaotropic agent-assisted, AQbD-guided RP-HPLC method for the simultaneous determination of rosuvastatin, atorvastatin, and ezetimibe: a rapid, robust, and green approach
Article References: Ihnatsevych, Y., Piponski, M., Oleshchuk, O., Rezk, M. R., Sulyma, M., Sverstyuk, A., Horyn, M., Kryskiw, L., & Logoyda, L. (2026). A chaotropic agent-assisted, AQbD-guided RP-HPLC method for the simultaneous determination of rosuvastatin, atorvastatin, and ezetimibe: a rapid, robust, and green approach. BMC Chemistry. https://doi.org/10.1186/s13065-026-01944-5
Image Credits: AI Generated
DOI: 10.1186/s13065-026-01944-5
Keywords: RP-HPLC, Analytical Quality by Design, rosuvastatin, atorvastatin, ezetimibe, chaotropic agent, Box-Behnken design, green analytical chemistry, pharmaceutical quality control, method validation, BMC Chemistry, chaotropic
News Source: Bethany Barker. (October 29, 2026). Green HPLC Method Simultaneously Measures Three Cholesterol Drugs in Minutes. Scienmag.
