A computer program (DryLab® MP) is described that allows restricted multi-parameter mapping for any number (or kind) of separation variables, based on only a few experiments. Multi-parameter computer simulation can be used to develop an high-performance liquid chromatographic method from the beginning, or it can be used to enhance a method developed by other means, e.g., by trial-and-error, single-parameter mapping, etc. The software can also be used to evaluate (and improve) method ruggedness. Finally, various problems (column-to-column variability, change of retention with ambient temperature fluctuations, experimental errors, etc.) that are commonly encountered during routine operation can be handled in the same general way. Examples of these various applications are given.

Computer simulation was used to optimize high-performance liquid chromatography of phenol and its chloro and nitro derivatives. On the basis of two linear gradient runs of different steepness (RP-18—water + methanol + 1% acetic acid), several simulated gradient runs allowed the optimum gradient programme and flow-rate to be chosen so that the time of analysis could be considerably shortened. Good agreement between simulated and experimental chromatograms was obtained in spite of changes in experimental conditions.

Brief review of currently available expert system and simulation software approaches.

Use of DryLab programs as the core of a systematic method development strategy.

Requirements for new pharmaceutical products and their impact on applications of high-performance liquid chromatography (HPLC) are discussed. The strengths and weaknesses of HPLC in this context are evaluated and compared with current trends and expectation in separation science.