Eco-friendly stability-indicating chromatographic methods with integrated molecular docking and ADMET evaluation for...

Currently, many researchers strive to create eco-conscious methods for drug separation to avoid hazardous solvents. In line with this objective, this study focuses on developing two green chromatographic methods, TLC and UPLC, to determine the mixture of carvedilol (CAR) and ivabradine (IVA) used for controlling stable angina symptoms, along with their oxidative degradates. The TLC method employed toluene: methanol: ammonia (8:2:0.2, by volume) as a mobile phase and silica gel plates as the stationary phase, with detection at 270.0 nm using concentration ranges of 0.5-8.0 μg/band for each drug. The optimized UPLC method utilized a mobile phase of ethanol: 0.1% triethylamine adjusted by acetic acid to pH 6.4 (40:60 v/v) on an Agilent Poroshell C18 (150 mm × 3 mm) column, with a 0.3 mL/min flow rate at 30°C and fluorimetric detection at 285.0 nm excitation and 330.0 nm emission, with linearity of 0.2-12.0 μg/mL for both drugs. Green assessment of the proposed methods with 82 and 78 green Eco-scores, AGREE score values of 0.77 and 0.72 for UPLC and TLC methods, respectively were performed. Moreover, statistical comparison of the proposed methods with reported and official methods was conducted. Additionally, structure elucidation, molecular docking and ADMET assessment of the degradates were successfully performed.