Experimental design for the rapid selection of separation conditions for methyl and propyl parahydroxybenzoate, phenylephrine hydrochloride and chlorphenamine maleate by ion-pair liquid chromatography

Methyl and propyl parahydroxybenzoate (MPHB, PPHB), phenylephrine hydrochloride (PE) and chlorphenamine maleate (CPM) are often combined as ingredients in cough-syrups. Due to distinct chemical structures, pKa values among other chemical properties are different. This may result in a particular chromatographic behaviour on ion-pair reversed-phase liquid chromatographic (LC) systems. A face-centred central composite design was applied to study the impact of four LC mobile phase parameters and parameter interactions on the retention of these four compounds. The mobile phase parameters studied were the concentration of methanol as organic modifier, the concentration of sodium dioctylsulphosuccinate (SDSS) as counter-ion, the concentration of dimethyloctylamine (DMOA) as competitive base and the pH. By means of the proposed design, mathematical regression models and response surface plots were calculated, which could predict the compounds' retention times with good statistical reliability. Adequate combination of the most relevant of these mobile phase parameters enabled complete chromatographic separations within short times of analysis