Artificial Neural Network Prediction of Retention of Amino Acids in Reversed-Phase HPLC under Application of Linear Organic Modifier Gradients and/or pH Gradients

A multi-layer artificial neural network (ANN) was used to model the retention behavior of 16 o-phthalaldehyde derivatives of amino acids in reversed-phase liquid chromatography under application of various gradient elution modes. The retention data, taken from literature, were collected in acetonitrile–water eluents under application of linear organic modifier gradients (φ gradients), pH gradients, or double pH/φ gradients. At first, retention data collected in φ gradients and pH gradients were modeled separately, while these were successively combined in one dataset and fitted simultaneously. Specific ANN-based models were generated by combining the descriptors of the gradient profiles with 16 inputs representing the amino acids and providing the retention time of these solutes as the response. Categorical “bit-string” descriptors were adopted to identify the solutes, which allowed simultaneously modeling the retention times of all 16 target amino acids. The ANN-based models tested on external gradients provided mean errors for the predicted retention times of 1.1% (φ gradients), 1.4% (pH gradients), 2.5% (combined φ and pH gradients), and 2.5% (double pH/φ gradients). The accuracy of ANN prediction was better than that previously obtained by fitting of the same data with retention models based on the solution of the fundamental equation of gradient elution.