Development of quantitative structure-retention relationship models to improve the identification of leachables in...

Quantitative structure-retention relationship (QSRR) models can be used to predict the chromatographic retention time of chemicals and facilitate the identification of unknown compounds, notably with non-targeted analysis. In this study, QSRR models were developed from the data obtained for 178 pure chemical standards and four types of analytical columns (C18, phenylhexyl, pentafluorophenyl, cyano) in liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS). First, different data partitioning ratios and feature selection methods [random forest (RF) and support vector machine (SVM)] were tested to build models to predict chromatographic retention times based on 2D molecular descriptors. The internal and external performances of the non-linear (RF) and corresponding linear predictive models were systematically compared, and RF models resulted in better predictive capacities [p < 0.05, with an average PVE (proportion of variance explained) value of 0.89 ± 0.02] than linear models (0.79 ± 0.03). For each column, the resulting model was applied to identify leachables from actual plastic packaging samples. An in-depth investigation of the top 20 most intense molecular features revealed that all false-positives could be identified as outliers in the QSRR models (outside of the 95% prediction bands). Furthermore, analyzing a sample on multiple chromatographic columns and applying the associated QSRR models increased the capacity to filter false positives. Such an approach will contribute to a more effective identification of unknown or unexpected leachables in plastics (e.g. non-intended added substances), therefore refining our understanding of the chemical risks associated with food contact materials.