Revealing the differences in collision cross section values of small organic molecules acquired by different instrumental designs and prediction models

The number of open access databases containing experimental and predicted collision cross section (CCS) values is rising and leads to their increased use for compound identification. However, the reproducibility of reference values with different instrumental designs and the comparison between predicted and experimental CCS values is still under evaluation. This study compared experimental CCS values of 56 small molecules (Contaminants of Emerging Concern) acquired by both drift tube (DT) and travelling wave (TW) ion mobility mass spectrometry (IM-MS). The TWIM-MS included two instrumental designs (Synapt G2 and VION). The experimental TWCCSN2 values obtained by the TWIM-MS systems showed absolute percent errors (APEs) < 2% in comparison to experimental DTIMS data, indicating a good correlation between the datasets. Furthermore, TWCCSN2 values of [M − H]- ions presented the lowest APEs. An influence of the compound class on APEs was observed. The applicability of prediction models based on artificial neural networks (ANN) and multivariate adaptive regression splines (MARS), both built using TWIM-MS data, was investigated for the first time for the prediction of DTCCSN2 values. For [M+H]+ and [M − H]- ions, the 95th percentile confidence intervals of observed APEs were comparable to values reported for both models indicating a good applicability for DTIMS predictions. For the prediction of DTCCSN2 values of [M+Na]+ ions, the MARS based model provided the best results with 73.9% of the ions showing APEs below the threshold reported for [M+Na]+. Finally, recommendations for database transfer and applications of prediction models for future DTIMS studies are made. L. Belova acknowledges funding through a Research Foundation Flanders (FWO) fellowship (11G1821N). L. Bijlsma acknowledges his fellowship funded by “la Caixa” Foundation. The project that gave rise to these results also received the support of a fellowship from “la Caixa” Foundation (ID 10 0 010434). The fellowship code is LCF/BQ/PR21/11840012. Jesse Sterckx is acknowledged for helping with the measurements on the Synapt G2 system. This work received financial support also from the University Jaume I (UJI-B2020-19). The graphical abstract was created with BioRender.com, license no 2641–5211.