Generic and accurate prediction of retention times in liquid chromatography by post-projection calibration

Abstract

Abstract Retention time predictions from molecule structures in liquid chromatography (LC) are increasingly used in MS–based targeted and untargeted analyses, providing supplementary evidence for molecule annotation and reducing experimental measurements. Nevertheless, different LC setups (e.g., differences in gradient, column, and/or mobile phase) give rise to many prediction models that can only accurately predict retention times for a specific chromatographic method (CM). Here, a generic and accurate method is present to predict retention times across different CMs, by introducing the concept of post–projection calibration. This concept builds on the direct projections of retention times between different CMs and uses 33 external calibrants to eliminate the impact of LC setups on projection accuracy. Results data shows that after calibration, the median prediction error for each CM was in all cases below 3.8%. The number of true identities ranking first among their isomeric candidates increased by 11.1 to 113.3%. This work opens up broad possibilities for coordinating retention times between different laboratories and developing extensive retention databases.