Generalized calibration across LC-setups for generic prediction of small molecule retention times

Abstract

MotivationAccurate prediction of liquid chromatographic retention times from small molecule structures is useful for reducing experimental measurements and for improved identification in targeted and untargeted MS. However, different experimental setups (e.g. differences in columns, gradients, solvents, or stationary phase) have given rise to a multitude of prediction models that only predict accurate retention times for a specific experimental setup. In practice this typically results in the fitting of a new predictive model for each specific type of setup, which is not only inefficient but also requires substantial prior data to be accumulated on each such setup. ResultsHere we introduce the concept of generalized calibration, which is capable of the straightforward mapping of retention time models between different experimental setups. This concept builds on the database-controlled calibration approach implemented in PredRet, and fits calibration curves on predicted retention times instead of only on observed retention times. We show that this approach results in significantly higher accuracy of elution peak prediction than is achieved by setup-specific models.