Journal of Chromatography A, 886 (2000) 31–46 www.elsevier.com / locate / chroma Interpretive optimisation strategy applied to the isocratic separation of phenols by reversed-phase liquid chromatography with acetonitrile–water and methanol–water mobile phases a b b a, * ´ ´ ´ J.R. Torres-Lapasio , M. Roses , E. Bosch , M.C. Garcıa-Alvarez-Coque a ´ ´ ` Departament de Quımica Analıtica, Universitat de Valencia, c / Dr. Moliner 50, 46100 Burjassot, Spain b ´ ´ Departament de Quımica Analıtica, Universitat de Barcelona, Diagonal 647, 08028 Barcelona, Spain Received 17 January 2000; received in revised form 14 April 2000; accepted 25 April 2000 Abstract An optimisation protocol is presented for the resolution of complex mixtures in isocratic RPLC with binary mobile phases of organic solvent and water, which is based on the prediction of peak position and shape of the individual compounds. A good description of the retention was achieved through the application of statistical weights to the widely used linear or quadratic relationships between the logarithm of the retention factor (log k) and the organic solvent concentration in the mobile phase. The maximisation of the product of peak purities for each compound is shown as a competitive resolution strategy versus the worst value of a selectivity parameter. Peak purities allow one to associate a single resolution value to each compound, which is not affected by the identity of the interfering peaks. It is shown how when full resolution is not achieved with a single mobile phase, the same experimental data set (retention factors, asymmetries and efficiencies) can be used for finding two or three optimal complementary mobile phases (CMPs). Each CMP resolves fully some compounds in the mixture, while the remaining compounds can overlap among them. The elementary limiting resolutions, which measure the maximal separation degree for each compound, are also given as a useful guide in the selection of the elution conditions. A mixture of 13 phenols (phenol, chloro-, bromo-, nitro- and methyl-derivatives), eluted with acetonitrile–water or methanol–water mobile phases, is used to show the proposed methodology.  2000 Elsevier Science B.V. All rights reserved. Keywords: Optimization; Mobile phase composition; Peak purity; Phenols 1. Introduction optimisation strategies have been proposed to solve this problem. The most reliable and less time-con- The chromatographer is often concerned with the suming strategies apply resolution criteria based on separation of complex mixtures with a variable empirical or mechanistic models to describe the behaviour of their components, which makes good retention of solutes [1,2]. In reversed-phase liquid resolution sometimes extremely difficult. Several chromatography (RPLC), the elution is governed by the strength of solute–stationary phase and solute– mobile phase interactions. In binary mobile phases, *Corresponding author. Fax: 134-96-386-4436. numerous studies have established that an exponen- ´ E-mail address: celia.garcia@uv.es (M.C. Garcıa-Alvarez- Coque) tial decay yields a satisfactory description of the 0021-9673 / 00 / $ – see front matter  2000 Elsevier Science B.V. All rights reserved. PII: S0021-9673(00)00507-0