DryLab is used for the optimization of a model drug candidate and its degradation products. Accuracy of DryLab predicted retention times and resolution is compared with experimental values.

Multi-linear gradients have not been widely used in general-purpose HPLC in part because of experimental inconvenience in method development. Even with the use of computer modeling, identifying an optimum set of breakpoints has been done primarily by trial and error. Combining a spreadsheet with controllable chromatography modeling software has allowed to implement a systematic approach to bi- and tri-linear gradient optimization.

The development of the DryLab Software is a special achievement in analytical HPLC, which took place in the last 16 years. This paper tries to collect historical building stones and fundaments, which were laid down by the eminent work of Lloyd Snyder, John Dolan, Tom Jupille and many other enthusiastic scientist, from which DryLab has been put together to its state, where it is today. DryLab, being always a subject to changes, according to the needs of the user, never stopped to go on. Under the force of an ever changing science market, the development team of DryLab had to consider not just scientific improvements, but also new technological achievements, such as the introduction of Windows 1.0 and 3.1, later Windows NT and Windows 2000. The recent availability of new 32 bit program-ming tools allowed to carry out calculations of chromatograms much faster, to be able to show peak movements, which result of slight changes - for example - in eluent pH. DryLab is a great success of an interdisciplinary and intercontinental cooperation of many scientists.

For ionizable compounds such as organic acids, best results were obtained recently with simultaneous optimization of %B and pH, regardless of ionic strength or temperature. Changes in the pH of eluent A, adjusted to bracket the pK-values of acids (works also for bases and zwitterions), help to understand changes in critical resolution values due to shifts in peak positions.

A new strategy for neutral compounds, contained in many phytopharmaceuticals, was presented at HPLC 2001 in Maastricht by Molnár and Schmidt. The systematic work with kava pyrones and three different organic modifiers, methanol, acetonitrile and 2-propanol, by simultanously changing gradient slope versus temperature or gradient slope versus pH reveals the true composition of such mixtures.

The analytical chemist is interested to learn more about the influence of the experimental parameters on the resolution, but can often only rely on experiments, he was able to carry out in a given time in a project. There are however often as many chances to improve resolution in the "unexpected" direction as by varying them in the "expected" way. The tools for understanding the method and discover all chances for improved selectivity are the different resolution maps.