The simultaneous measurement of quaternary mixture in over-the-counter cold medications using sequential spectrophotometric resolution approach enhanced with in-lab sample enrichment.

A sequential spectrophotometric resolution technique (SSRT) was developed in this study without the use of systematic separation procedures to determine drug of a quaternary combination; caffeine (CAF), pseudoephedrine (PSE), doxylamine succinate (DOX), and paracetamol (PAR). Their presence in a tablet with a gap ratio of 3:3:1:150, respectively, and their overlapping spectra with low absorptivities make their resolution and determination impossible without prior separation. successive ratio subtraction technique (SRST) and constant multiplication method were used to solve these problems. Furthermore, an in-lab sample enrichment technique was applied to increase minor components concentration and consequently their absorbanses (CAF, PSE, and DOX). The D absorption spectra were generated by successive ratios followed by subtraction and multiplication of the constants. The maximum absorbances of the drugs tested, namely (CAF, PSE, DOX and PAR) were measured at wavelengths of 272.0, 257.0, 260.0, and 248.0 nm, respectively. The limits of detection (LOD) and limits of quantification (LOQ) were 0.021, 0.124, 0.186, 0.137 and 0.070, 0.414, 0.621, 0.456 (µg/mL), respectively. The linearitiy ranges (µg/mL) were 1.0-22.0, 1.0-24.0, 10.0-90.0 and 1.0-15.0 for CAF, PSE, DOX, and PAR, respectively. The International Conference on Harmonization (ICH) guidelines were applied for method validation, and the results obtained were within the limited parameters. The finding results were compared to official and/or published analytical methods to determine the procedure's reliability. It was noted that there was no actual difference in accuracy and precision between both meyhods. The proposed technique is sensitive, selective and economic;so it can be applied to the simultaneous analysis of these drugs in their commercial tablets and/or in quality-control laboratories.