Development and Validation of a Green HPLC Method for Simultaneous Determination of Paracetamol and Caffeine in Tablets

The present work describes the development and validation of HPLC method for simultaneous determination of Paracetamol and Caffeine in Pharmaceutical Tablet, which is green, rapid and efficient. The separation was performed by chromatography on a C18 column (150 × 4.6 mm, 5 µm) with an eco-friendly ethanol: water (30:70, v/v) mobile phase at a flow rate of 1.0 mL/min and PDA detection. The method exhibited good linear range of 5-50 µg/mL for paracetamol and 1-10 µg/mL for caffeine with correlation coefficient (R²) values > 0.999. The increased polarity of caffeine and reduced hydrophobic interactions with the C18 stationary phase caused reduced retention time and lower k' values, and was deemed as the cause of the poor retention. The detection limits for paracetamol and caffeine were 0.15µg/mL and 0.08µg/mL, respectively and the recovery percentages of 98.5% to 101.2% were obtained. The developed method was found to be highly green with a high AGREE greenness score of 0.82, better than the conventional acetonitrile- and methanol-based methods, and was successfully applied for routine quality control analysis of commercial pharmaceutical formulations.