Environmental benign RP-HPLC method for the simultaneous estimation of anti-hypertensive drugs using analytical quality by design

ABSTRACT Green analytical procedures replace harmful organic modifiers with green solvents without affecting chromatographic performance, enabling industries and research laboratories to develop green analytical methods. Benidipine hydrochloride (BEN) and Chlorthalidone (CHD) were used to treat hypertension. The literature indicates that no method for determining BEN and CHD combines RP-HPLC with green Analytical Quality by Design (AQbD) for long-term use. This study aimed to develop a green RP-HPLC for determining BEN and CHD by incorporating analytical quality by design with green chemistry principles. A central composite design was used for optimization, with 40% ethanol content and flow rate chosen as critical variables. Separation was achieved using Agilent Eclipse Plus (C18, 250 mm × 4.6 mm i.d, 5 μm) with a mobile phase of ethanol and potassium dihydrogen orthophosphate (orthophosphoric acid to 3.5) in a ratio of 40:60 v/v at 1 ml/min, detection wavelength at 230 nm. Retention times for CHD and BEN were 3.1 and 5.1 min, respectively. The concentration ranges for BEN and CHD were 3.2–4.8 μg/ml and 5.0–7.5 μg/ml, respectively. The proposed method was eco-friendly and assessed using green evaluation tools. Thus, AQBD and green technologies provide regular BEN and CHD analysis in pharmaceutical formulations without environmental impact. GRAPHICAL ABSTRACT