Alternating iterative regression method for dead time estimation from experimental designs

An indirect method for dead time (t ₀) estimation in reversed-phase liquid chromatography, based on a relationship between retention time and organic solvent content, is proposed. The method processes the retention data obtained in experimental designs. In order to get more general validity and enhance the accuracy, the information from several compounds is used altogether in an alternating regression fashion. The method was applied to nitrosamines, alkylbenzenes, phenols, benzene derivatives, polycyclic aromatic hydrocarbons and β-blockers, among other compounds, chromatographed in a cyano and several C18 columns. A comprehensive validation was carried out by comparing the results with those provided by the injection of markers, the observation of the solvent front and the homologous series method. It was also found that different groups of compounds yielded the same t ₀ value with the same column, which was verified in different solvent composition windows. The method allows improved models useful for optimisation or for other purposes, since t ₀ can be estimated with the retention data of the target solutes.