Rank analysis and simultaneous determination of acetylsalicylic acid, paracetamol, and caffeine in pharmaceuticals using second-order data and multivariate curve resolution-alternating least squares (MCR-ALS)

Mixtures of acetylsalicylic acid (ASA), paracetamol (PAR), and caffeine (CAF) have been successfully analyzed by constrained multivariate curve resolution-alternating least squares (MCR-ALS). The MCR-ALS methodology adequately exploits the second-order advantage which enables quantitation of analyte in the presence of unknown and uncalibrated interferences. The procedure simultaneously takes into account the spectroscopic and pH-dependent properties of the compounds, which leads to a higher selectivity. Specially, for CAF determination fully protonated or deprotonated forms of CAF are not dominant in the pH range of data acquisition but spectral changes with pH were recorded and used for accurate determination of CAF. Furthermore, quantitative determination of an analyte in a complex mixture is performed using a synthetic solution as standard containing only the analyte of interest. Even in the presence of the rank deficiencies, in most cases accurate quantitation with relative errors in prediction lower than 5 % was obtained. The procedure was successfully applied to the analysis of real samples (pharmaceuticals) using synthetic external standards. Percent relative errors of 4.03, 3.26, and 5.85 were obtained for ASA, PAR, and CAF, respectively, in A.C.A tablets and 4.49 and 2.75 for PAR and CAF, respectively in Novafen capsules.