A Green High‐Performance Liquid Chromatographic Approach for the Simultaneous Determination of Paracetamol and Aspirin Alongside Their Toxic and Major Impurities

Abstract

ABSTRACT Regulatory agencies, including the US Food and Drug Administration and the International Conference on Harmonization, are currently focusing on the assessment of various pharmaceuticals in the presence of their contaminants. Consequently, a green high‐performance liquid chromatographic method was developed, optimized, and validated for the simultaneous separation and quantitation of a quaternary mixture of Paracetamol (PAR) and Aspirin (ASP) in the presence of the toxic impurity of PAR, 4‐aminophenol, and the major impurity of ASP, salicylic acid (SA). The optimized separation of the studied compounds was performed on a Kinetex C18 column (100 mm × 4.6 mm I.D., particle size 2.6 µm) at ambient temperature using 0.05 M sodium dodecyl sulfate 0.1% ortho‐phosphoric acid:methanol (70.0:30.0, v/v) with a flow rate of 1.0 mL/min, followed by UV detection at 230.0 nm. Linear regressions were achieved at concentrations ranging from 1.0–50.0 µg/mL for paracetamol and salicylic acid and from 1.0–30.0 µg/mL for aspirin and 4‐aminophenol. The suggested approach was confirmed to comply with ICH regulations and was effectively utilized for the quantification of a PAR and ASP binary mixture in a dosage form, achieving a distinct separation of the two medicines from their contaminants. Finally, the eco‐friendliness of the suggested approach was validated via the Analytical Eco‐scale, the Green Analytical Procedure index, and the Analytical GREEnness metric approach tools.